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630 Study Matches
Preventing Retaliatory Gun Violence in Violently Injured Adults
Nicholas Thomson - Nicholas.Thomson@vcuhealth.org
NCT04813185
Inclusion Criteria:
* They receive treatment in the hospital for a violence-related injury (e.g., gunshot wound)
* They are 18 years or older
* They are English speaking
* They are eligible for BTG services (which includes living within the BTG catchment area for the hospital; Richmond City and neighboring counties)
Exclusion Criteria:
* Non-English speaking
* Age \<18
* Prisoners BEHAVIORAL: Bridging the Gap
Violence
Colorectal Health Research Champions
Hunley, Rachel - rachel.hunley@vcuhealth.org
Sheppard, Vanessa, B.
NCT04812743
HM20017398
Inclusion Criteria:
the individual is > 30 years of age
• They are literate
• They are/were directly or indirectly impacted by colorectal cancer and interested in becoming a champion for colorectal cancer research. To participate in a chat hosted by the CHRC the inclusion criteria is:
• adult of any gender
• over 30 years of age. Exclusion Criteria for chat hosted by the CHRC: -Those < 30 years of age
Behavioral: Colorectal Health Research Champions
Cancer of Colon, Cancer of Rectum, Rectum, Colon
Prevention
Crystalloids Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS)
Mason, Jessica - jessica.mason1@vcuhealth.org
de Wit, Marjolein
NCT03434028
HM20013528
Inclusion Criteria:
• Age ? 18 years
• A suspected or confirmed infection (broadly defined by administration or planned administration of antibiotics)
• Sepsis-induced hypotension defined as systolic blood pressure < 100 mmHg or MAP < 65 mmHg after a minimum of at least 1 liter of fluid (*Fluids inclusive of pre-hospital fluids; blood pressure must be below any known or reported pre-morbid baseline).
Exclusion Criteria:
• More than 4 hours elapsed since meeting inclusion criteria or 24 hours elapsed since admission to the hospital
• Patient already received 3 liters of intravenous fluid (includes prehospital volumes)
• Unable to obtain informed consent
• Known pregnancy
• Hypotension suspected to be due to non-sepsis cause (e.g. hemorrhagic shock)
• Blood pressure is at known or reported baseline level
• Severe Volume Depletion from an acute condition other than sepsis. In the judgment of the treating physician, the patient has an acute condition other than sepsis causing (or indicative) of *severe volume depletion; Examples include: Diabetic ketoacidosis, high volume vomiting or diarrhea, hyperosmolar hyperglycemic state, and nonexertional hyperthermia (heat stroke); severe is defined by the need for substantial intravenous fluid administration as part of routine clinical care
• Pulmonary edema or clinical signs of new fluid overload (e.g. bilateral crackles, new oxygen requirement, new peripheral edema, fluid overload on chest x-ray)
• Treating physician unwilling to give additional fluids as directed by the liberal protocol
• Treating physician unwilling to use vasopressors as directed by the restrictive protocol.
• Current or imminent decision to withhold most/all life-sustaining treatment; this does not exclude those patients committed to full support except cardiopulmonary resuscitation
• Immediate surgical intervention planned such that study procedures could not be followed
• Prior enrollment in this study
Drug: Early Vasopressors, Drug: Early Fluids,
drug: Ringer's (hartmann's) lactate solution,
drug: Plasmalyte (crystalloid) solution,
drug: Normal (0.9%, isotonic) saline solution,
drug: Norepinephrine
Septic Shock, Symptoms, Signs, and lll-Defined Conditions (780-799)
Fluid management, Sepsis-induced hypotension, vasopressors
IBP-9414 for the Prevention of Necrotizing Enterocolitis - The Connection Study
Subotic, Aleksander - aleksandar.subotic@vcuhealth.org
Moores, Russell, Ray
NCT03978000
HM20018843
Inclusion Criteria:
• Gestational age at birth of 23 weeks+0 days to 32 weeks+0 days
• Birth weight 500-1500g
• ? 48 hours of age
• Written informed consent from the subject?s legally authorized representative (LAR)
Exclusion Criteria:
• Participation in any other interventional clinical trial
• Infants in extremis to whom no further intensive care is offered by attending neonatologist
• Infants with, or at a high probability for, early onset sepsis
• Infants with recognized chromosomal anomalies
• Congenital or acquired gastrointestinal disease
• Earlier or planned administration of formulas, foods or supplements that contain added live bacteria
• Infants with known positive maternal HIV status
Drug: IBP-9414, Drug: Placebo,
drug: Ibp-9414
Necrotizing Enterocolitis, Certain Conditions Originating in the Perinatal Period (760-779)
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
Lantis, Kristin - kllantis@vcu.edu
Maher, Keri
NCT04530565
HM20021870
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT) and ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1
Registry of Patients With a Diagnosis of Spinal Muscular Atrophy (SMA) (RESTORE)
Novartis Gene Therapies - novartis.email@novartis.com
Johnson, Nicholas, E
NCT04174157
HM20015046
Inclusion Criteria:
* Patients treated with OAV-101 with a genetically confirmed diagnosis of SMA regardless of the date of diagnosis.
* Appropriate consent/assent has been obtained for participation in the registry
Exclusion Criteria:
• Currently enrolled in an interventional clinical trial involving an investigational medicinal product to treat SMA. Note: Patients who are participating in a Compassionate Use Program (CUP) for OAV-101 (Zolgensma) such as a Managed Access Program (MAP), an Expanded Access Program (EAP), Single Patient Investigational New Drug (IND) (SPI) or Named Patient Program (NPP) are eligible to enroll in the registry regardless of the date of a genetic or clinical diagnosis of SMA.
OTHER: Prospective observational registry, DRUG: Zolgensma
Spinal Muscular Atrophy (SMA)
Post Approval Study for Treatment of Drug-resistant Adult and Pediatric Primary FSGS Using the LIPOSORBER® LA-15 System (FSGSALLAGE)
Ayaka Kitamura - Ayaka.Kitamura1@kaneka.co.jp
NCT04065438
Inclusion Criteria:
A patient is deemed suitable for inclusion in the study if the patient has nephrotic syndrome associated with primary FSGS when:
• Standard treatment options, including corticosteroid and/or calcineurin inhibitors, are unsuccessful or not well tolerated and the patient's glomerular filtration rate (GFR) ≥ 45 ml/min/1.73 m2.
or
• The patient is post renal transplantation.
Exclusion Criteria:
General Exclusion Criteria
• Patient is greater than 75 years of age at the start of the treatment period or less than 22
• The patient is unwilling or unable to sign and date the informed consent
• Pregnant, lactating, or planning to become pregnant prior to completing the study (Note: The safety of the use of LIPOSORBER® in pregnant women has not been studied. There may be unknown risks to an embryo/fetus. Sexually active women of childbearing potential should avoid pregnancy during the use of the LIPOSORBER device and throughout the study duration.)
• Unable or unwilling to comply with the follow-up schedule
• Simultaneously participating in another investigational drug or device study
• Body weight \< 15 kg (33.1 lbs) Medical Exclusion Criteria
• Currently being administered ACE inhibitors that cannot be withheld for at least 24 hours prior to each apheresis treatment (Note: The time period to withhold ACE inhibitors should be prolonged, if determined by the treating physician, considering each individual's renal function and the biological half-life of the ACE-inhibitor currently in use.)
• Currently being administered antihypertensive drugs other than ACE inhibitors (e.g., ARBs) that cannot be withheld on the day of apheresis until after the procedure
• Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis
• Hypersensitivity to dextran sulfate, heparin, or ethylene oxide
• Adequate anticoagulation cannot be achieved due to severe hemophilia, severe hemorrhage diathesis, severe gastrointestinal ulcers, or are recipients of vitamin K antagonist medications
• Extracorporeal circulation therapy with LIPOSORBER® LA-15 System cannot be tolerated due to severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute apoplexy, severe uncontrollable hypertension, or severe uncontrollable hypotension Note: Severe uncontrollable hypotension/hypertension indicates the cases with systolic and/or diastolic blood pressure ≤ 5th percentile for age, gender, and height.
• Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease
• Functional thyroid disease or liver abnormalities
• Unresolved systemic or local infection that could affect the clinical study outcomes
DEVICE: LIPOSORBER® LA-15
Focal Segmental Glomerulosclerosis
FSGS, Liposorber
Study to Test OBI-3424 in Patients With T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LBL)
Weir, Caryn, R - cweir@vcu.edu
Maher, Keri
NCT04315324
HM20021956
Inclusion Criteria:
* Patients must have a diagnosis of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) based on World Health Organization (WHO) classification. Patients with relapsed/refractory T-cell lymphoblastic lymphoma are eligible if lymphoblasts are \>= 5% in the bone marrow or in the peripheral blood by morphology or flow cytometry
* Patients must have evidence of acute leukemia in their peripheral blood or bone marrow. Patients must have \>= 5% lymphoblasts in the peripheral blood or bone marrow within 14 days prior to registration. Patients with only extramedullary disease are not eligible
* Patients ≥ 18 years of age must be refractory to or have relapsed following a standard induction chemotherapy. Patients \< 18 years of age must have relapsed or must be refractory after 2 or more chemotherapy cycles (example: induction and consolidation)
* A standard chemotherapy induction regimen is defined as any program of treatment that includes:
* Vincristine and corticosteroids plus at least one more chemotherapy agent
* Cytarabine and anthracycline, or
* High dose cytarabine (defined as at least 1 gr/m\^2 per individual dose unless adjustments were required for renal/liver function)
* Patients must have no evidence of central nervous system disease within 28 days prior to registration based on cerebrospinal fluid (CSF) studies. Patients with clinical signs or symptoms consistent with central nervous system (CNS) involvement must have a lumbar puncture which is negative for CNS involvement; the lumbar puncture must be completed within 28 days prior to registration. Patients with CNS1 or CNS2 are eligible; however patients with CNS3 are not eligible
* Note that the patients may receive intrathecal chemotherapy with the initial lumbar puncture. This may count as the first dose of intrathecal therapy required as part of the study
* Prior nelarabine therapy is not required. In addition, for patients ≥ 18 years of age who received nelarabine during initial induction or post-remission treatment are eligible only if the physician does not feel they would benefit from other, multi-agent chemotherapy
* Patients must not have had chemotherapy or investigational agents within 14 days prior to registration except for corticosteroids, oral 6-mercaptopurine, oral methotrexate, vincristine, intrathecal chemotherapy, or hydroxyurea. For participants who have received radiation therapy, at least 7 days must have elapsed from the end of radiation prior to registration and participants must not currently be experiencing toxicities from radiation therapy
* Patients must not have undergone allogeneic hematopoietic transplant within 90 days prior to registration
* Patients must have no evidence of active \>= grade 2 acute graft versus host disease (GVHD) or moderate or severe limited chronic GVHD. Patients must have no history of extensive GVHD of any severity within 90 days prior to registration. Patients who are post-transplant must be off calcineurin inhibitors for at least 21 days to be eligible. Extensive GVHD is defined as 1) generalized skin involvement or 2) localized skin involvement and/or hepatic dysfunction plus liver histology or cirrhosis or involvement of eye or minor salivary organ or oral mucosa or any other target organ
* Patients must be \>= 12 years of age
* Patients ≥ 16 years of age must have a Zubrod Performance Status of 0-3. Patients \< 16 years of age must have a Lansky score of ≥ 50
* Patients must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) within 14 days prior to registration
* Patients ≥ 18 years of age must have creatinine clearance \> 30 mL/min within 14 days prior to registration according to the Cockcroft Gault equation
* Patients 12-17 years of age must have adequate renal function within 14 days prior to registration defined as serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) according to age or a calculated estimated glomerular filtration rate (eGFR) (based on Schwartz formula) or radioisotope glomerular filtration rate (GFR) ≥ 50ml/min/1.73 m\^2
* Patients must have direct bilirubin =\< 1.5 x institutional upper limit of normal (ULN) within 14 days prior to registration
* Patients must have alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) or =\< 5.0 x ULN (if thought to be related to leukemic involvement) within 14 days prior to registration
* Prothrombin time (PT)/partial thromboplastin time (PTT)/ fibrinogen (as clinically indicated for example but not limited to history of bleeding or active bleeding, concern for disseminated intravascular coagulation) (within 14 days prior to registration to obtain baseline measurements)
* From metabolic panel (comprehensive or basic): sodium, potassium, chloride, carbon dioxide (CO2), and blood urea nitrogen (BUN) (within 14 days prior to registration to obtain baseline measurements)
* Patients must be able to safely discontinue use of strong inhibitors/inducers of CYP3A4 or PgP-g-p and must be able to safely discontinue use of naproxen for 48 hours before and after each dose of OBI-3424
* Patients with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test within 6 months prior to registration. (HIV viral load testing is required only for patients with known HIV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients with evidence of chronic hepatitis B virus (HBV) infection may be eligible provided that they have an undetectable HBV viral load within 28 days prior to registration. Patients may be currently receiving HBV treatment. (HBV viral load testing is required only for patients with known HBV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients with known history of hepatitis C virus (HCV) infection may be eligible provided that they have an undetectable HCV viral load within in 28 days prior to registration. Patients may be currently receiving treatment. (HCV viral load testing is required only for patients with known HCV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients must not have a known history of prolonged QT interval by Fridericia (QTcF) (interval \> 450 msec for males; \> 470 msec for females). Patients that had transient prolongation of QTc secondary to medications or electrolyte abnormalities are not excluded if the QTc normalized and remain within acceptable QTcF range (interval \> 450 msec for males; \> 470 msec for females). Additionally, suspected medications should be no longer required or used, and electrolyte abnormalities must have normalized
* Patients must not be pregnant or nursing due to the teratogenic potential of the drug used on this study. Females of reproductive potential must have a negative serum pregnancy test within 14 days prior to registration. Women/men of reproductive potential must have agreed to use an effective contraceptive method during and up to 6 months after treatment. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Patients must not have other active malignancies for which they have received treatments within 6 months prior to registration excluding localized malignancies that do not require systemic treatment
* Patients must agree to have bone marrow and blood specimens submitted for MRD testing
* Patients must be offered the opportunity to participate in specimen banking. With patient consent, residuals from specimens submitted will be retained and banked for future research
* Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with fedral, local, institutional and Central Institutional Review Board (CIRB) guidelines unless they are unable to provide consent based on age (\< 18 years) or based on impaired decision-making capabilities. For patients \< 18 years of age or with impaired decision making capabilities, parents or other legally authorized representatives must sign and give informed consent on behalf of study participants in accordance with applicable federal, local, institutional and CIRB regulations
* As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* This trial will use a slot reservation system to enroll the Phase I portion of the study. Patients planning to enroll at this phase of the study must first have a slot reserved in advance of the registration. All site staff will use OPEN to create a slot reservation DRUG: AKR1C3-activated Prodrug AST-3424, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Computed Tomography
Recurrent T Acute Lymphoblastic Leukemia, Refractory T Acute Lymphoblastic Leukemia, Refractory T Lymphoblastic Lymphoma, T Lymphoblastic Lymphoma
EAP for subjects receiving Idecabtagene Vicleucel That is Nonconforming for Commercial Release
Hall, Charles, E. - hallce3@vcu.edu
Simmons, Gary, L.
NCT04771078
HM20021892
Inclusion Criteria:
• Had a participant-specific batch of Idecabtagene vicleucel (ide-cel) manufactured intended for commercial treatment; however, the final manufactured product was nonconforming and did not meet commercial release criteria
• Remanufacturing is deemed not feasible or clinically inappropriate per assessment of the treating physician in discussion with the participant
• Clinically stable
Exclusion Criteria:
• Has a hypersensitivity to the active substance or to any of the excipients
• No experience of a significant worsening in clinical status that would, in the opinion of the treating physician, either increase the risk of Adverse Events associated with lymphodepleting chemotherapy, or exclude them from treatment with nonconforming Idecabtagene vicleucel (ide-cel)
• Has any condition and/or laboratory abnormality that places the participant at unacceptable risk if he/she were to participate in the Expanded Access Protocol based on the Investigator's judgement Other protocol-defined inclusion/exclusion criteria apply
Biological: Nonconforming idecabtagene vicleucel,
drug: Idecabtagene vicleucel, Modality: Immunotherapy
Multiple Myeloma
BB2121, Multiple Myeloma, Expanded Access, idecabtagene vicleucel, nonconforming, CAR T, EAP, Pre-Approval Access
A Phase 1B/2 Study of RP1 in Solid Organ Transplant Patients With Advanced Cutaneous Malignancies (ARTACUS)
Clinical Trials at Replimune - Clinicaltrials@replimune.com
Poklepovic, Andrew, S
NCT04349436
HM20021229
Key
• Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol and understand the risk to their organ allograft.
• Patients with histologically or cytologically confirmed recurrent, locally advanced or metastatic (to skin, soft tissue or lymph nodes) cutaneous malignancies, including CSCC, basal cell carcinoma, Merkel cell carcinoma, and melanoma
• Patients must have progressed following local resection, prior radiation, topical or systemic therapies.
• Documentation from the patient's transplant physician confirming that the patient's allograft is stable.
• Patients for whom surgical or radiation treatment of lesions is contraindicated.
• At least 1 lesion that is measurable and injectable by study criteria (tumor of ≥1cm in longest diameter or ≥1.5 cm in shortest diameter for lymph nodes).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Anticipated life expectancy \> 6 months
• Baseline ECG without evidence of acute ischemia.
• All patients must consent to provide archived or newly obtained tumor material (either formalin-fixed, paraffin-embedded \[FFPE\] block or 20 unstained slides). Key
• Prior treatment with an oncolytic therapy.
• Patients with visceral metastases.
• Patients with active herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
• Patients with a history of organ graft rejection within 12 months.
• Had systemic infection requiring intravenous (IV) antibiotics or anti-virals, or other serious infection within 60 days prior to dosing.
• Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g., acyclovir) unless for organ allograft preservation.
• Patients requiring CTLA-4-Ig medications.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments beyond that required for maintenance allograft rejection prevention. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that requires only hormone replacement, or psoriasis that does not require systemic treatment.
• Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
• Any history of transplant-related viral infections, such as BKV, EBV or CMV, within 3 months of study entry. Patients with a history of hepatitis B or C virus must have undetectable viral load within 3 months of study entry.
• Patients with a condition requiring an increase in the patient's usual immunosuppressive medications within 60 days of study treatment.
• Known active CNS metastases and/or carcinomatous meningitis.
Inclusion Criteria:
• Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol and understand the risk to their organ allograft.
• Patients with histologically or cytologically confirmed recurrent, locally advanced or metastatic (to skin, soft tissue or lymph nodes) cutaneous malignancies, including CSCC, basal cell carcinoma, Merkel cell carcinoma, and melanoma
• Patients must have progressed following local resection, prior radiation, topical or systemic therapies.
• Documentation from the patient's transplant physician confirming that the patient's allograft is stable.
• Patients for whom surgical or radiation treatment of lesions is contraindicated.
• At least 1 lesion that is measurable and injectable by study criteria (tumor of ≥1cm in longest diameter or ≥1.5 cm in shortest diameter for lymph nodes).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Anticipated life expectancy \> 6 months
• Baseline ECG without evidence of acute ischemia.
• All patients must consent to provide archived or newly obtained tumor material (either formalin-fixed, paraffin-embedded \[FFPE\] block or 20 unstained slides). Key
Exclusion Criteria:
• Prior treatment with an oncolytic therapy.
• Patients with visceral metastases.
• Patients with active herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
• Patients with a history of organ graft rejection within 12 months.
• Had systemic infection requiring intravenous (IV) antibiotics or anti-virals, or other serious infection within 60 days prior to dosing.
• Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g., acyclovir) unless for organ allograft preservation.
• Patients requiring CTLA-4-Ig medications.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments beyond that required for maintenance allograft rejection prevention. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that requires only hormone replacement, or psoriasis that does not require systemic treatment.
• Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
• Any history of transplant-related viral infections, such as BKV, EBV or CMV, within 3 months of study entry. Patients with a history of hepatitis B or C virus must have undetectable viral load within 3 months of study entry.
• Patients with a condition requiring an increase in the patient's usual immunosuppressive medications within 60 days of study treatment.
• Known active CNS metastases and/or carcinomatous meningitis.
BIOLOGICAL: RP1, intra-tumoral injection, oncolytic virus
Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, Basal Cell Carcinoma, Melanoma
Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP)
William Meurer - wmeurer@med.umich.edu
Peberdy, Mary Ann
NCT04217551
HM20019809
Inclusion Criteria:
* Coma after resuscitation from out of hospital cardiac arrest
* Cooled to \<34 deg C with 240 minutes of cardiac arrest
* Definitive temperature control applied
* Age ≥ 18 years
* Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours
* Enrollment within 6 hours of initiation of cooling
Exclusion Criteria:
* Hemodynamic instability
* Pre-existing neurological disability or condition that confounds outcome determination
* Pre-existing terminal illness, unlikely to survive to outcome determination
* Planned early withdrawal of life support
* Presumed sepsis as etiology of arrest
* Prisoner DEVICE: Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma
Mindful Moms Randomized Control Trial
Patricia Kinser, PhD - kinserpa@vcu.edu
Kinser, Patricia, A
NCT04886856
HM20021720
Inclusion Criteria:
• pregnant woman at 12-26 weeks gestation at baseline visit;
• defined as minority (e.g., Black/ African American, Hispanic/ Latino, Native American, etc) and/or annual household income at qualification level for Women, Infants, \& Children \[WIC\] benefits in Virginia and/or educational attainment ≤high school education;
• ≥age 18;
• current depressive symptoms, as defined by a score ≥7 on the Edinburgh Postnatal Depression Scale (EPDS);
• able to read, write, and understand English;
• has not been told by a healthcare provider to avoid physical activity;
• has not engaged in a consistent (once/week or more) yoga-based practice during the current pregnancy.
Exclusion Criteria:
Does not meet the inclusion criteria above. BEHAVIORAL: Mindful Moms, BEHAVIORAL: Prenatal Education
Depression
pregnancy
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer (AIM-NIVO)
McFadden, Faith - mcfaddenfr@vcu.edu
Poklepovic, Andrew, S
NCT03816345
HM20022009
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI). Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements PROCEDURE: Biospecimen Collection, BIOLOGICAL: Nivolumab
Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm, Multiple Sclerosis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sjogren Syndrome, Systemic Lupus Erythematosus, Systemic Scleroderma, Ulcerative Colitis
Nonconforming Lisocabtagene Maraleucel Expanded Access Protocol
Hall, Charles, E. - hallce3@vcu.edu
Simmons, Gary, L.
NCT04400591
HM20022052
Inclusion Criteria:
• Subject and/or LAR must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
• Subject has relapsed and/or refractory large B-cell lymphoma and is, per the treating physician assessment, eligible for treatment with lisocabtagene maraleucel per the approved prescribing information.
• Subject is ? 18 years of age at the time of signing the informed consent form.
• Subject had a specific batch of lisocabtagene maraleucel manufactured intended for commercial treatment; however, the final manufactured product did not meet commercial release criteria.
• Remanufacturing (eg, repeat leukapheresis and manufacturing) is deemed not feasible or clinically inappropriate per assessment of the treating physician in discussion with the subject.
• Subject is clinically stable, has recovered from any toxicities prior to receiving lymphodepleting chemotherapy, and has adequate bone marrow function to receive lymphodepleting chemotherapy. The treating physician is advised to contact Medical Monitor in the event there is any concern regarding administration of lymphodepleting chemotherapy.
• Females of childbearing potential must:
• Have a negative pregnancy test as verified by the treating physician within 7 days prior to the first dose of lymphodepleting chemotherapy following institutional testing methodology practices. This applies even if the subject practices true abstinence from heterosexual contact.
• Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective method from screening until at least 12 months after the nonconforming lisocabtagene maraleucel administration.
• Agree to abstain from breastfeeding during study participation and for at least 12 months following nonconforming lisocabtagene maraleucel administration.
• There are insufficient exposure data to provide any recommendation concerning the duration of contraception and the abstaining from breastfeeding following treatment with lisocabtagene maraleucel. Any decision regarding contraception and breastfeeding after infusion should be discussed with the treating physician.
• Male subjects must:
• Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 12 months after nonconforming lisocabtagene maraleucel administration even if the subject has undergone a successful vasectomy.
• There are insufficient exposure data to provide any recommendation concerning the duration of contraception following treatment with lisocabtagene maraleucel. Any decision regarding contraception after infusion should be discussed with the treating physician
• Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells for usage in other individuals for at least 1 year following nonconforming lisocabtagene maraleucel administration.
Exclusion Criteria:
• Subject has a hypersensitivity to the active substance or to any of the excipients.
• Subject should not experience a significant worsening in clinical status that would, in the opinion of the treating physician, either increase the risk of adverse events associated with lymphodepleting chemotherapy, or exclude them from treatment with nonconforming lisocabtagene maraleucel.
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness, sociologic or geographic condition that would prevent the subject from participating in the Expanded Access Protocol complying with protocol requirements in the Investigator's judgement.
• Subject has any condition and/or laboratory abnormality that places the subject at unacceptable risk if he/she were to participate in the Expanded Access Protocol based on the Investigator's judgement
• Pregnant or nursing women or has intention of becoming pregnant during the study.
• Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study).
• Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of pretreatment evaluation
• Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of nonconforming lisocabtagene maraleucel administration.
• Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD)
• Use of the following:
• Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 72 hours prior to nonconforming lisocabtagene maraleucel administration. Physiologic replacement, topical, and inhaled steroids are permitted.
• Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ? 300 mg/m2)given after leukapheresis to maintain disease control must be stopped ? 7 days prior to lymphodepleting chemotherapy.
• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of LD chemotherapy. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to lymphodepleting chemotherapy.
• Donor lymphocyte infusions within 6 weeks of nonconforming lisocabtagene maraleucel administration.
Biological: Nonconforming Lisocabtagene Maraleucel
Lymphoma, Large B-Cell, Diffuse
Expanded Access, JCAR017, Lisocabtagene Maraleucel, CAR T, nonconforming,, relapsed/refractory diffuse large B cell lymphoma, nonconforming lisocabtagene mareleucel
Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery (FLORA-5)
Clinical Operations - ClinicalTrialDisclosures@oncoquestinc.com
Randall, Leslie
NCT04498117
HM20021341
Major
• Adults 18 years old or older.
• Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.
• Histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
• Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator). Debulking surgery must be optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).
• Preoperative serum CA- 125 levels ≥ 50 U/mL.
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/µL
• Platelets greater than or equal to100,000/µL
• Hemoglobin greater than or equal to 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).
• Adequate liver function:
• Bilirubin < 1.5 times upper limit normal (ULN)
• Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
• Albumin >3.5 g/dL
• Adequate renal function: a. Creatinine less than or equal to1.5 times ULN
• ECOG Performance Status of 0 or 1. Major
• BRCA1 or BRCA2 germline gene mutation test result with:
• Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or
• Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or
• Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy.
• Subjects with mucinous adenocarcinoma and low- grade adenocarcinoma.
• Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment (C1D1 for Cohort 1 or C4D1 for Cohort 2).
• Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment.
• Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
• Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G).
• Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. (Note: Premedication with corticosteroids per institutional standard of care is allowed.)
• Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
• Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP- ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.
Inclusion Criteria:
• Adults 18 years old or older.
• Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.
• Histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
• Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator). Debulking surgery must be optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).
• Preoperative serum CA- 125 levels ≥ 50 U/mL.
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/µL
• Platelets greater than or equal to100,000/µL
• Hemoglobin greater than or equal to 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).
• Adequate liver function:
• Bilirubin < 1.5 times upper limit normal (ULN)
• Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
• Albumin >3.5 g/dL
• Adequate renal function: a. Creatinine less than or equal to1.5 times ULN
• ECOG Performance Status of 0 or 1. Major
Exclusion Criteria:
• BRCA1 or BRCA2 germline gene mutation test result with:
• Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or
• Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or
• Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy.
• Subjects with mucinous adenocarcinoma and low- grade adenocarcinoma.
• Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment (C1D1 for Cohort 1 or C4D1 for Cohort 2).
• Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment.
• Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
• Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G).
• Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. (Note: Premedication with corticosteroids per institutional standard of care is allowed.)
• Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
• Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP- ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.
Biological: Oregovomab, Drug: Paclitaxel, Drug: Carboplatin, Biological: Placebo
Carcinoma, Ovarian Epithelial, Ovarian Neoplasms, Ovarian Cancer, Ovarian Serous Adenocarcinoma, Fallopian Tube Neoplasms, Fallopian Tube Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma, Peritoneal Cancer, Peritoneal Carcinoma, Peritoneal Neoplasms
Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma
Schaefer, Melissa - schaeferm@vcu.edu
Alesi, Erin, R.
NCT04671667
HM20022077
Inclusion Criteria:
* Patient must be between 18 and 79 years of age
* Patient must have locoregionally recurrent or second primary HNSCC (oral cavity, oropharynx, larynx, hypopharynx) in a previously radiated field
* Patient must have undergone surgery with gross total resection and must be randomized within 8 weeks of surgery
* Patients must have high risk disease defined as:
* Positive margins and/or extra nodal extension (ENE)
* Positive margins are defined as malignancy at or within 1 mm of the margin. High grade dysplasia (i.e. carcinoma in situ) at the margin is also considered positive
* ENE may be either gross or microscopic
* Patient must have a PD-L1 Combined Positive Score (CPS) \>= 1 in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Testing can be done locally as long as it is done in a CLIA certified laboratory. This testing must be on the tumor specimen from the resection of the patient's recurrent or second primary HNSCC
* Patient must have had prior radiation to the area of recurrent or second primary tumor. This is defined as \> 50% of the presurgical tumor volume having previously received a dose of \> 45 Gy as determined by the treating radiation oncologist
* Patient must have completed prior radiation a minimum of 6 months prior to randomization
* Patient must not have any evidence of distant disease based on baseline imaging done within 28 days prior to randomization
* Patient must not have received anti-PD-1/PD-L1 therapy for recurrent disease. If the patient received anti-PD-1/PD-L1 therapy as part of initial upfront curative intent treatment (either as part of definitive non-surgical therapy or in the adjuvant setting) in the past, the last dosage of anti-PD-1/PD-L1 therapy must have been given greater than one year prior to randomization
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab or chemotherapy if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A patient of childbearing potential is someone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on study treatment, and continue for 120 days after the last dose of study treatment
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 28 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to protocol randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 28 days prior to protocol randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 28 days prior to protocol randomization)
* Creatinine clearance \> 30 ml/min using the Cockcroft-Gault formula (obtained =\< 28 days prior to protocol randomization)
* Patient must not have a current active infection that requires systemic treatment at time of randomization
* Patient must not have a history of non-infectious pneumonitis requiring steroids within 3 years prior to randomization
* Patient must not have a history of solid organ transplant or stem cell transplant
* Patient must not be on immunosuppressive medication within 7 days prior to randomization, EXCEPT for the following: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. Patients with New York Heart Association class III or IV heart failure are not eligible
* Patient must not have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed
* Patient must not have severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
* Patient must not have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as they have not been HIV-infected with a history of Kaposi sarcoma and/or multicentric Castleman disease
* Patient must not have a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
* NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Pembrolizumab, RADIATION: Proton Beam Radiation Therapy
Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 3
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04916340
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency BEHAVIORAL: Muscular Strength Training Group, BEHAVIORAL: Muscular Fitness Training Group
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 1
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04916327
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency DIETARY_SUPPLEMENT: Antioxidant, DIETARY_SUPPLEMENT: Placebo
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
Study of Immune Globulin Intravenous (Human) GC5107 in Pediatric Subjects With Primary Humoral Immunodeficiency
Hyejoo Kim - hyejoo.kim@gccorp.com
Zhao, Wei
NCT04565015
HM20021702
Inclusion Criteria:
• Subject must be ≥ 2 to < 17 years of age, at the time of signing the informed consent
• Pediatric subject has a confirmed and documented clinical diagnosis of Primary Humoral Immunodeficiency, including hypogammaglobulinemia or agammaglobulinemia
• Subject who has received 300 - 900 mg/kg of IGIV therapy at 21 or 28 day intervals for at least 3 months prior to this study
• Subject who has at least 2 documented plasma IgG trough level of ≥ 500 mg/dL at two infusion cycles (21 or 28 days) within 12 months prior to enrollment
• Subject who is willing to comply with all requirements of the protocol
Exclusion Criteria:
• Subject who has a history of clinically significant reactions or hypersensitivity to IGIV or other injectable forms of IgG
• Subject who has IgA deficiency and is known to have antibodies to IgA
• Subject who has secondary immunodeficiency
• Subject who has participated in another clinical study (other than an IGIV study) within 3 weeks prior to screening
• Subject who has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency or isolated IgA deficiency, or who has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
• Subject who has received blood products other than human albumin or human immune globulin within 6 months prior to enrollment
Biological: GC5107
Primary Immune Deficiency
A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV) (DAISY)
Study Contact - JNJ.CT@sylogent.com
NCT04583280
Inclusion criteria:
• The participant weighs within greater than or equal to (>=) 2.4 kilograms (kg) and less than or equal to (<=) 24.6 kg
• Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
• The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as <75 percent [%] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility
• The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
• Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease Exclusion criteria:
• The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
• Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
• Known personal or family history of Long QT Syndrome or sudden cardiac death
• Presence of repetitive ventricular premature contractions (>10/minutes [min]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening
• The participant weighs within greater than or equal to (>=) 2.4 kilograms (kg) and less than or equal to (<=) 24.6 kg
• Each participant's parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative(s) has/have signed an informed consent form (ICF) indicating that (s)he understands the purpose of, and procedures required for, the study; is willing for their child to participate in the study; with regards to the concomitant medication, the lifestyle consideration and study procedures and assessments to be performed by the parent(s)/caregiver(s) as well as those by the investigator/study site personnel
• The participant has an acute respiratory illness with at least 1 of the signs/symptoms within 24 hours prior to start of screening and at screening, as evaluated by the investigator in Upper respiratory tract infection: nasal congestion or rhinorrhea; and Lower respiratory tract infection: increased respiratory effort (as evidenced by subcostal, intercostal or tracheosternal retractions, grunting, head bobbing, nasal flaring, or tachypnea), wheezing, cough, cyanosis, or apnea; and systemic/general: feeding difficulties (defined as <75 percent [%] intake of normal food amounts); dehydration; fever; disturbed sleep, or disturbed activity level (irritable/restless/agitated/less responsive). Cough or wheezing cannot be the only LRTI sign/symptom present, that is, at least one other LRTI sign/symptom needs to be present for eligibility
• The time of onset of RSV signs/symptoms to the anticipated time of randomization must be less than or equal to (<=) 3 days. Onset of signs/symptoms is defined as the time of the day (or part of the day if time of the day cannot be specified) the parent(s)/caregiver(s) became aware of the first sign and/or symptom consistent with respiratory or systemic/general manifestation of signs/symptoms of RSV infection. The time of sign/symptom onset has to be assessed as accurately as possible
• Participants are otherwise healthy or have (a) risk factor(s) for severe RSV disease Exclusion criteria:
• The participant has had either confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (test positive) during the four weeks prior to randomization, or close contact with a person with COVID-19 (test confirmed or suspected SARS CoV-2 infection) within 14 days prior to randomization
• Confirmed QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval greater than (>) 450 milliseconds (msec) per the machine read parameter result at screening. Presence of an abnormal QTcF interval should be confirmed by repeat electrocardiogram (ECG) recording during screening
• Known personal or family history of Long QT Syndrome or sudden cardiac death
• Presence of repetitive ventricular premature contractions (>10/minutes [min]), second- or third-degree heart block, or complete or incomplete left bundle branch block, or complete right bundle branch block per the machine read ECG result at screening. Presence of any of the above abnormalities should be confirmed by repeat ECG recording during screening
Drug: Rilematovir, Drug: Rilematovir X mg/kg, Drug: Placebo
Respiratory Tract Infections
Examining the Impact of Exercise Training on Vascular Dysfunction in Individuals With Mental Health Disorders - Study 2
Ryan Garten, PhD - rsgarten@vcu.edu
NCT04922762
Inclusion Criteria:
* apparently healthy and free of overt cardiovascular, pulmonary, or metabolic disease
* for PTSD group, a score of ≥ 33 on PCL-5 checklist
* for GAD group, a score of ≥ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
* for Healthy Control group, a score of ≤ 10 on the GAD-7 self-report scale and \< 33 on the PCL-5 checklist
Exclusion Criteria:
* taking medications that could influence cardiovascular function
* current smokers who have recently quit smoking
* illicit drug use or excessive alcohol consumption
* pregnant women
* significant calorie restriction or vitamin/mineral deficiencies
* limited English proficiency BEHAVIORAL: Moderate Intensity, Normal Volume Exercise Training, BEHAVIORAL: High Intensity, Normal Volume Exercise Training, BEHAVIORAL: Moderate Intensity, High Volume Exercise Training
Peripheral Vascular Diseases
cardiovascular disease, vascular function, PTSD, GAD, Oxidant
A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes
Medical Information - medicalinfo@vrtx.com
Levy, Marlon
NCT04786262
HM20021228
Key
Inclusion Criteria:
* Clinical history of T1D with \> 5 years of duration of insulin dependence
* At least two episodes of documented severe hypoglycemia in the 12 months prior to enrollment
* Stable diabetic treatment
* Consistent use of continuous glucose monitor (CGM) for at least 3 months before Screening and willingness to use CGM for the duration of the study
Key Exclusion Criteria:
-Prior islet cell transplant, organ transplant, or cell therapy
Other protocol defined Inclusion/Exclusion criteria may apply BIOLOGICAL: VX-880
Diabetes Mellitus, Type 1, Impaired Hypoglycemic Awareness, Severe Hypoglycemia
A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1)
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or - ClinicalTrials.gov@lilly.com
Koch, William, C
NCT04427501
HM20022495
Inclusion Criteria:
• Are currently not hospitalized. (Not applicable to participants in treatment arm 22.)
• Have one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion. (Not applicable to participants in treatment arm 22.)
• Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
• Are males or females, including pregnant females who agree to contraceptive requirements
• Understand and agree to comply with planned study procedures
• Agree to the collection of nasopharyngeal swabs and venous blood. (Not applicable to participants in treatment arms 20-21.)
• The participant or legally authorized representative give signed informed consent and/or assent Participants in treatment arms 7-9, 13-14, and 18-21 ONLY
• Are greater than or equal to (≥)18 years of age and must satisfy at least one of the following at the time of screening
• Are pregnant
• Are ≥65 years of age
• Have a body mass index (BMI) ≥35
• Have chronic kidney disease (CKD)
• Have type 1 or type 2 diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment or
• Are ≥55 years of age AND have:
• cardiovascular disease (CVD), OR
• hypertension, OR
• chronic obstructive pulmonary disease (COPD) or other chronic respiratory disease
• Are 12-17 years of age (inclusive) AND satisfy at least one of the following at the time of screening
• Are pregnant
• Have a body mass index (BMI) ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
• Have sickle cell disease
• Have congenital or acquired heart disease
• Have neurodevelopmental disorders, for example, cerebral palsy
• Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
• Have asthma or reactive airway or other chronic respiratory disease that requires daily medication for control
• Have type 1 or type 2 diabetes
• Have chronic kidney disease
• Have immunosuppressive disease, or
• Are currently receiving immunosuppressive treatment Participants in treatment arm 22 ONLY
• Are 0 (≥ 32 weeks gestational age AND ≥ 1.5 kilograms [kg]) to 17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening
• Are pregnant
• Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
• Have sickle cell disease
• Have congenital or acquired heart disease
• Have neurodevelopmental disorders, for example, cerebral palsy, autism, or Down syndrome (FAIR Health 2020; Spreat et al. 2020)
• Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
• Have asthma, cystic fibrosis, reactive airways disease or other chronic respiratory disease that requires daily medication for control
• Have type 1 or type 2 diabetes
• Have chronic kidney disease
• Have immunosuppressive disease, or
• Are currently receiving immunosuppressive treatment, or
• Are less than (<) one year of age.
• Have one or more COVID-19 symptoms
• Shortness of breath/difficulty breathing
• Fever
• Sore throat
• Nausea
• Diarrhea
• Tiredness
• Headache
• New loss of taste
• Nasal congestion/runny nose
• Chills
• Stomachache
• Vomiting
• Cough
• Muscle/body aches and pain
• New loss of smell
• Poor appetite or poor feeding (in babies) Participants in treatment arm 23 ONLY: Must have first positive result sample of current SARS-CoV-2 viral infection ≤3 days prior to start of treatment administration. Participant can have COVID previously and still meet criteria for this addendum. Positive result needs to be from a current infection. Are 0 (≥ 38 weeks gestational age and ≥ 3.3 kg) to <12 years of age at the time of screening, or are 12 to 17 and weighing <40 kg; and
• Have mild to moderate COVID-19 disease, including one or more COVID-19 symptoms within the last 7 days
• Shortness of breath/difficulty breathing
• Fever
• Sore throat
• Nausea
• Diarrhea
• Tiredness
• Headache
• New loss of taste
• Nasal congestion/runny nose
• Chills
• Malaise
• Vomiting
• Cough
• Muscle/body aches and pain
• New loss of smell
• Poor appetite or poor feeding (in babies under 1 year old)
Exclusion Criteria:
• Have oxygen saturation (SpO2) less than or equal to (≤)93 percent (%) on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) less than (<)300, respiratory rate greater than or equal to (≥)30 per minute, heart rate ≥125 per minute due to COVID-19
• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
• Have known allergies to any of the components used in the formulation of the interventions
• Have hemodynamic instability requiring use of pressors within 24 hours of randomization
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
• Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 29 days
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study
• Have a history of a positive SARS-CoV-2 test prior to the one serving as eligibility for this study
• Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
• Have received treatment with a SARS-CoV-2 specific monoclonal antibody
• Have received convalescent COVID-19 plasma treatment
• Have participated in a previous SARS-CoV-2 vaccine study or have received a SARS-CoV-2 vaccine
• Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Mothers who are breast feeding Participants in Treatment Arm 22 ONLY
• Have a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) in the opinion of the investigator
• Are currently hospitalized for treatment of COVID-19. Other reasons for hospitalization are acceptable. Participants in treatment arm 23 ONLY
• SpO2 ≤ 93% on room air at sea level, or while on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity, respiratory rate ≥30 per minute, and heart rate ≥125 per minute due to COVID-19 (FDA February 2021)
• Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
• Have known allergies to any of the components used in the formulation of the interventions
• Have hemodynamic instability requiring use of pressors within 24 hours of randomization
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
• Have any co-morbidity requiring surgery within 7 days, or that is considered life-threatening within 29 days
• Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study.
• Have received treatment with a SARS-CoV-2 specific monoclonal antibody or remdesivir within 90 days before dosing.
• Have received convalescent COVID-19 plasma treatment within 90 days before dosing
• Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Are currently pregnant or breast feeding
Drug: LY3819253, Drug: LY3832479, Drug: LY3853113, Drug: Placebo
COVID-19
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial (EQUATE)
Lantis, Kristin - kllantis@vcu.edu
Yazbeck, Victor, Y
NCT04566328
HM20022350
Inclusion Criteria:
* STEP 0 - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
* STEP 0 - Patient must have newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria
* STEP 0 - Patient must agree to register to the mandatory REVLIMID Risk Evaluation and Mitigation Strategy (RevREMS) program and be willing and able to comply with the requirements of RevREMS
* STEP 0 - Patient must be able to undergo diagnostic bone marrow aspirate following preregistration.
* NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies for clonoSEQ Assay
* NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from the Clonality (ID) test within fourteen (14) days of receipt and reconciliation of fresh bone marrow specimen to the submitting institution
* STEP 1 - Patient must meet all eligibility criteria in STEP 0 with exception of allergy requirement
* STEP 1 - Institution must have received the Clonality (ID) test results from Adaptive Biotechnologies and dominant sequences were identified
* STEP 1 - Patient must have standard risk MM as defined by the Revised International Staging System (RISS) stage I or II
* NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH). Presence of del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these, including any other findings, are standard risk
* R-ISS stage
* Stage I: ISS stage I \[beta2 macroglobulin \< 3.5 mg/L, albumin \> 3.5 g/dL\] AND standard-risk CA AND normal LDH
* Stage II: Not R-ISS stage I or III
* Stage III: ISS stage III \[beta2 macroglobulin \> 5.5 mg/L\] AND high-risk CA OR high LDH (\> upper limit of normal) \[patients with stage III are ineligible\]
* STEP 1 - Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to registration:
* \>= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
* \>= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis
* Involved free light chain \>= 10 mg/dL or \>= 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (\< 0.26 or \> 1.65)
* Monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease)
* STEP 1 - Patients must have a serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28 days prior to registration. In addition, a bone marrow biopsy and/or aspirate is required within 28 days if bone marrow is being followed for response
* NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is \>= 200 mg/24 hr. Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response
* NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine. Measurable disease in the serum is defined as having a serum M-spike \>= 1 g/dL. Measurable disease in the urine is defined as having a urine M-spike \>= 200 mg/24 hr
* STEP 1 - Calculated creatinine clearance \> 30 mL/min (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Untransfused platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (obtained =\< 14 days prior to Step 1 registration)
* STEP 1 - Patient must have received no more than one cycle (28 days or less) of prior chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided there are no residual toxicity related to radiation and blood counts meet the study requirements. Radiation treatment must be completed at least 14 days prior to Step 1 registration
* STEP 1 - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* STEP 1 - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* STEP 1 - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* STEP 1 - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* STEP 1 - Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Patients must not have evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within 6 months prior to Step 1 registration
* STEP 1 - Patient may have a history of current or previous deep vein thrombosis (DVT) or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
* STEP 1 - Patients with a history of chronic obstructive pulmonary disease (COPD) must have FEV1 testing done within 28 days prior to Step 1 registration and the forced expiratory volume in 1 second (FEV1) must be \> 50% of predicted normal
* STEP 2 - Institution must have received Tracking (MRD) test results from Adaptive Biotechnologies
* STEP 2 - Patient must have completed the Step 1 Induction phase of this protocol without experiencing progression
* STEP 2 - Patient must be registered to Step 2 within 8 weeks of completing Step 1 Induction Treatment, counting from last day of completion of last cycle
* STEP 2 - Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
* STEP 2 - Any adverse event(s) related to Step 1 Induction Treatment must have resolved to grade 2 or less
* STEP 2 - Hemoglobin \>= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Platelet count \>= 50,000/mm\^3 (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Calculated creatinine clearance \>= 30 mL/min (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - Total bilirubin =\< 1.5 x ULN (Institutional upper limit of normal) (obtained within 14 days prior to Step 2 randomization)
* STEP 2 - ALT and AST \< 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
* STEP 0 - Patient must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products
* STEP 1 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 1 registration to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point,
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* STEP 1 - Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception (for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment
* STEP 1 - Patient must not have peripheral neuropathy \>= grade 2 on clinical examination or grade 1 with pain at time of Step 1 registration
* STEP 1 - Patient must not have any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
* STEP 1 - Patient must not have moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
* NOTE: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to register
* STEP 1 - Patient must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol
* NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* STEP 2 - Patient must not have received any non-protocol therapy outside of the assigned Step 1 Induction treatment including stem cell transplant
* STEP 2 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
* Has achieved menarche at some point,
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* STEP 2 - Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception (for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment DRUG: Bortezomib, BIOLOGICAL: Daratumumab and Hyaluronidase-fihj, DRUG: Dexamethasone, DRUG: Lenalidomide, OTHER: Quality-of-Life Assessment
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma
Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
Megan Scott - bmtctn1904@emmes.com
NCT04965597
Inclusion Criteria:
• Patient must be >= 1.0 year of age and less than 50.0 years of age at the time of enrollment (i.e. patient must have celebrated their 1st birthday when enrolled and must NOT have celebrated their 50th birthday when enrolled; 49.99 years)
• Underlying BMFD treatable by allogenic HCT
• Shwachman-Diamond syndrome
• Criteria for Diagnosis:
• A pathogenic mutation(s) for Shwachman-Diamond syndrome
• For those patients tested but lacking a genetic mutation they must meet both **** criteria below:
• Exocrine pancreatic dysfunction as defined by at least one of the following:
• Pancreatic isoamylase below normal (age >= 3 years old), OR
• Fecal elastase < 200, AND
• Bone marrow failure as evidence by at least one of the following:
• Intermittent or persistent neutropenia (absolute neutrophil count < 1,500/uL), OR
• Hypo-productive anemia with a hemoglobin concentration below the age-related adjusted norms, OR
• Unexplained macrocytosis, OR
• Platelet count < 150,000/uL without alternative etiology, OR
• Hypocellular bone marrow
• Indications for HCT:
• Severe neutropenia (absolute neutrophil count [ANC] < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 eligibility review committee (ERC). In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet the indications for transplant listed above
• Diamond Blackfan Anemia
• Criteria for Diagnosis:
• A pathogenic mutation for Diamond Blackfan anemia
• For those patients tested but lacking a genetic mutation the patient must meet the first *** criteria and at least one of the subsequent *** criteria listed below:
• History of deficiency of erythroid precursors in an otherwise cellular bone marrow AND,
• Reticulocytopenia, OR
• Elevated adenosine deaminase activity, OR
• Elevated hemoglobin F, OR
• Macrocytosis, OR
• Congenital anomalies
• Indications for HCT:
• Red blood cell (RBC) transfusion dependent anemia despite an adequate trial of steroids; OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Congenital Sideroblastic anemia
• Criteria for Diagnosis:
• A pathogenic mutation(s) for sideroblastic anemia
• For those patients tested but lacking a genetic mutation:
• Presence of ringed sideroblasts in the bone marrow excluding acquired causes of ringed sideroblasts such as lead poisoning & zinc toxicity
• Indications for HCT:
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• GATA2 mutation with associated marrow failure
• Criteria for Diagnosis: ** A pathogenic mutation(s) for GATA2
• Indications for HCT:
• Severe neutropenia (ANC < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC. In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet indications for transplant listed above
• SAMD9 or SAMD9L disorders
• Criteria for Diagnosis: ** A pathogenic mutation(s) for SAMD9 or SAMD9L
• Indications for HCT:
• Severe neutropenia (ANC < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Congenital amegakaryocytic thrombocytopenia
• Criteria for Diagnosis:
• A pathogenic mutation(s) for congenital amegakaryocytic thrombocytopenia.
• For those patients tested but lacking a genetic mutation the patient must meet criteria below:
• Thrombocytopenia early in life, AND
• History of bone marrow demonstrating megakaryocyte hypoplasia
• Indications for HCT:
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Neutropenia defined as an ANC < 500/uL, OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
• Paroxysmal nocturnal hemoglobinuria
• Criteria for Diagnosis:
• Paroxysmal nocturnal hemoglobinuria (PNH) clone size in granulocytes >= 10%, AND
• Complement mediated intravascular hemolysis with an elevated LDH (above institutional upper limits of normal)
• Indications for HCT:
• PNH with thrombosis despite adequate medical management, OR
• PNH with intravascular hemolysis requiring transfusion support despite adequate medical management, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC. In addition, patients with PNH and cytopenias may be considered for the protocol eligibility following review by protocol 1904 ERC
• An undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified (excluding PNH) will be eligible for this clinical trial following approval by Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1904 ERC * A BMFD with a known genetic mutation but not listed above will be eligible for this clinical trial following approval by BMT CTN 1904 ERC
• Patient and/or legal guardian must sign informed consent prior to initiation of conditioning for BMT CTN 1904
• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence
• Note: The following patients MUST be reviewed by the BMT CTN 1904 ERC in order to determine if they are eligible for this trial:
• All patients with Shwachman-Diamond syndrome, Diamond Blackfan anemia, congenital sideroblastic anemia, and congenital amegakaryocytic thrombocytopenia who have had genetic testing and lack a genetic mutation
• All patients with an undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified, excluding PNH
• All patients with a BMFD and a known genetic mutation that is not listed above
• All patients with GATA2 mutation and associated marrow failure
• All patients with SAMD9 or SAMD9L disorders
• There may be circumstances where a treating physician will consider a transplant for a patient with a BMFD who does not meet all the criteria listed under "indications for HCT". In these situations, treating physicians may submit their patient to the BMT CTN 1904 ERC for review in order to determine if the patient is eligible for this clinical trial based on additional clinical or laboratory information
• Many patients with BMFD can have bone marrow evaluations that raise concern for possible myelodysplastic syndrome (MDS) including but not limited to dysplastic bone marrow evaluations or cytogenetic abnormalities. However, in patients BMFD these findings are not necessarily diagnostic or consistent with MDS. Therefore, given the complexities of diagnosing MDS in patients with BMFD, all patients with bone marrow evaluations concerning for possible MDS should be submitted to the ERC for review to confirm or exclude MDS. This is particularly important as we do not want to exclude potentially eligible patients due to an incorrect diagnosis of MDS
• HLA-MATCHED RELATED DONOR: HLA-matched sibling: Must be a minimum HLA-6/6 matched to the recipient at HLA-A, -B (serologic typing) and DRB1 (high-resolution typing)
• HLA-MATCHED RELATED DONOR: HLA-matched related (phenotypic match): Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing.
• HLA-MATCHED RELATED DONOR: If a genetic mutation is known for the patient, the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must be screened for the same genetic mutation if clinically appropriate and should be confirmed to not have the same genetic disease (this does not include patients with PNH). Consult the protocol team with questions
• HLA-MATCHED RELATED DONOR: If a patient has an undefined BMFD (a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified), the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must have an evaluation as directed by the treating physician to confirm that the donor does not have the same underlying disease. This will include a complete blood count (CBC) with differential and potentially a bone marrow evaluation or other studies as directed by the treating physician
• UNRELATED DONOR: Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing
• UNRELATED DONOR: Mismatched for a single HLA-class 1 allele (HLA-A, -B, or -C) by high-resolution typing; OR
• UNRELATED DONOR: Mismatched for a single HLA DQB1 allele or antigen by high-resolution typing * Note: donor patient (DP) matching per institutional practice
• DONOR SELECTION RECCOMENDATIONS: in the case where there are multiple donor options, donors should be selected based on the following priority numbered below:
• Unaffected fully HLA-matched sibling
• Unaffected fully phenotypically HLA-matched related donor
• Fully HLA-matched unrelated donor
• Unrelated donor with single allele or antigen level mismatch at DQB1
• Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C)
Exclusion Criteria:
• Patients with idiopathic aplastic anemia, Fanconi anemia, dyskeratosis congenita, and congenital neutropenia
• Patients with MDS as defined by the World Health Organization (WHO) or leukemia
• Prior allogeneic HCT
• Patient's weight =< 10.0 kg (actual body weight and adjusted body weight) at time of study enrollment
• Lansky (patients < 16 years of age) or Karnofsky (patients >= 16 years of age) performance < 70%
• Left ventricular ejection fraction < 50% by echocardiogram or multi-gated acquisition (MUGA) scan * For patients unable to obtain a left ventricular ejection fraction, left ventricular shortening fraction of < 26%
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) < 50%, forced expiratory volume (FEV)1 < 50% predicted, and forced vital capacity (FVC) < 50% predicted
• For patients unable to perform pulmonary function tests (PFTs) due to age or developmental delay: oxygen (O2) saturation < 92% on room air
• On supplemental oxygen
• Estimated creatinine clearance < 60 mL/minute/1.73m^2 (estimated per institutional practice)
• Dialysis dependent
• Conjugated bilirubin > 2 x ULN for age (upper limit of normal [ULN], unless attributable to Gilbert's syndrome)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x ULN for age, or
• Fulminant liver failure or cirrhosis
• Iron overload - This exclusion criterion only applies to patients who are considered at risk for hepatic or cardiac iron overload. Therefore, not all patients enrolled on this protocol will undergo formal hepatic or cardiac iron assessment
• For patients >= 18 years with a history of significant transfusions defined as >= 8 packed red blood cell transfusions per year for >= 1 year or have received >= 20 packed red blood cell transfusions (lifetime cumulative) will require formal hepatic and cardiac iron measurement. In addition, patients with a prior history of hepatic or cardiac iron overload will also require formal assessment for iron overload. Patients are excluded if:
• Hepatic iron content >= 8 mg Fe/g dry weight by liver magnetic resonance imaging (MRI) using a validated methodology (such as T2 * MRI or ferriscan) or liver biopsy per institutional practice
• Cardiac iron content < 25 msec by cardiac T2 * MRI
• For patients < 18 years old with a history of significant transfusions defined as >= 8 packed red blood cell transfusions per year for >= 1 year or have received >= 20 packed red blood cell transfusions (lifetime cumulative) will require formal hepatic iron measurement. In addition, patients with a prior history of liver iron overload will also require formal assessment for iron overload. Patients are excluded if:
• Hepatic iron content >= 8 mg Fe/g dry weight by liver MRI using a validated methodology (such as T2 * MRI or ferriscan) or liver biopsy per institutional practice
• Uncontrolled bacterial infection within 1 week of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Uncontrolled viral or fungal infection within 30 days of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Positive for human immunodeficiency virus (HIV)
• Presence of clinically significant anti-donor human leukocyte antigen (HLA)-antibodies per institutional practice
• Prior solid organ transplant
• Patients with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ
• Demonstrated lack of compliance with prior medical care as determined by referring physician
• Females who are pregnant or breast-feeding
• Known hypersensitivity to treosulfan or fludarabine
• Known life-threatening reaction (i.e. anaphylaxis) to Thymoglobulin that would prohibit use for the patient as this study requires use of the Thymoglobulin preparation of anti-thymocyte globulin (ATG)
Drug: Treosulfan, Drug: Fludarabine Phosphate, Drug: Tacrolimus, Drug: Methotrexate, Biological: Lapine T-Lymphocyte Immune Globulin, Procedure: Peripheral Blood Stem Cell Transplantation, Procedure: Allogeneic Bone Marrow Transplantation, Other: Quality-of-Life Assessment
Bone Marrow Failure Syndrome, Congenital Amegakaryocytic Thrombocytopenia, Congenital Pure Red Cell Aplasia, Hereditary Sideroblastic Anemia, Myeloid Neoplasms With Germline GATA2 Mutation, Paroxysmal Nocturnal Hemoglobinuria, Shwachman-Diamond Syndrome
Bone Marrow Failure Disorders, HSCT, Treosulfan, Unrelated donor, Matched donor, mismatched donor, transplant
A Study to Determine Frequency of DNA-repair Defects in Men With Metastatic Prostate Cancer (PREVALENCE)
Study Contact - Participate-In-This-Study@its.jnj.com
Paul, Asit, K.
NCT03871816
Inclusion Criteria:
• Diagnosis of metastatic (Stage IV) prostate cancer (PC), confirmed by either biopsy of a metastatic tumor site or history of localized disease supported by metastatic disease on imaging studies (that is [i.e.], clearly noted in hospital/clinical records)
• Signed Informed consent form (ICF)
• No condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example [e.g.], compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Willing to provide a saliva, blood, and/or archival tumor tissue sample for genomic analysis
• No prior poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) for the treatment of prostate cancer
• No prior DNA-repair gene defect test results from a Janssen sponsored interventional trial
Other: Saliva, Blood, or and/or Archival Tumor Tissue Collection and Analysis
Metastatic Prostate Cancer
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Gowda, Madhu, S
NCT01790152
HM20000463
Inclusion Criteria:
Study Strata I, II, and III are closed for further patient entry as of March 31, 2021. The study remains open for existing medical record submission of Stratum IV
* STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
* Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
* STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma \[P9404, high-risk DFCI 95-01\] or Hodgkin lymphoma \[P9425/P9426\])
* STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
* STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest \[also includes fields directed towards the neck, upper abdomen, or spine\], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
* STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's \[COG?s\] Statistics and Data Center \[SDC\] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (IRB) specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims; patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution)
* STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
* STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM III: OSTEOSARCOMA SURVIVORS
* Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
* Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
* Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
* \< 31 years of age at time of initial osteosarcoma diagnosis
* Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
* No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction \>= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction \>= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
* Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m\^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
* No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
* No exposure to DRZ at any point in time
* All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3
* Individuals diagnosed with cancer prior to age 21 years, who required treatment with chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after completing anti-cancer-therapy for at least 1 year
* Must have screening echocardiograms for heart function as part of cancer therapy and off-therapy evaluations available (Digital Imaging and Communications in Medicine \[DICOM\] format). Images from Video Home System (VHS) tapes and reports only (without images) are not suitable
* Cannot have a known history of congenital heart disease (patent foramen ovale remain eligible) or underlying genetic syndrome associated with abnormal cardiovascular development or health (e.g., down syndrome)
* Based on echocardiography, must have either left ventricular fractional shortening =\< 28.0% or ejection fraction =\< 50.0% on at least two occasions, with at least one of these measurements occurring after cancer therapy completion and be in the absence of sepsis or any uncontrolled infection
* If the fractional shortening or ejection fraction criteria is only met on one occasion, this must be after cancer therapy completion, be in the absence of sepsis or any uncontrolled infection, and the patient must have subsequently started on chronic medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme \[ACE\]-inhibitor, angiotensin receptor blocker) lasting at least 6 months
* For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Assessment of Therapy Complications, OTHER: Laboratory Biomarker Analysis, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma in Remission, Leukemia in Remission, Lymphoblastic Lymphoma, Osteosarcoma, Recurrent Leukemia, Recurrent Lymphoma, Recurrent Malignant Neoplasm
Safety, Tolerability and Effectiveness of ALVR105 in Kidney Transplant Recipients
Fenner, Shawn - shawn.fenner@vcuhealth.org
Gupta, Gaurav
NCT04605484
HM20020745
Inclusion Criteria:
• Patients who had a kidney transplant performed greater than or equal to 28 days prior to enrollment
• At least 1 identified, suitably matched Posoleucel (ALVR105) cell line for infusion is available. (If a matching Posoleucel line is not available, the following patient data will be collected: demographic data and human leukocyte antigen [HLA] type.)
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female patient is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• She is a woman of non-childbearing potential (WONCBP) as defined in the protocol
• She is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in the protocol during the study treatment period and for at least 90 days after the last dose of study treatment. The Investigator should evaluate the potential for contraceptive method failure.
Exclusion Criteria:
• Undergone allogeneic hematopoietic cell transplantation
• Evidence or history of graft versus host disease (GVHD) or cytokine release syndrome (CRS).
• Uncontrolled or progressive bacterial or fungal infections
• Known or presumed pneumonia
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Pregnant or lactating or planning to become pregnant.
• Weight <40 kg.
• Patients who received, or planned to receive abatacept or belatacept, within 3 months of screening
Biological: Posoleucel (formerly known as ALVR105) cells, Biological: Placebo (visually identical to Posoleucel),
drug: Viralym-m (alvr105)
BK Virus Nephropathy, BK Virus Infection, Infectious and Parasitic Diseases (001-139)
Virtual Walking Intervention for Neuropathic Pain in Spinal Cord Injury (VRWalk)
Hannah Palanchi - hannah.palanchi@vcuhealth.org
Trost, Zina
NCT05005026
HM20020719
Inclusion Criteria:
• The study will recruit individuals with complete injury (American Spinal Injury Association [ASIA] classification A) with lumbar, paraplegic, or low tetraplegic (C5-C7) injury. Additional criterial will include:
• persistent NP symptoms that are of daily severity of at least 4/10
• endorsement of more than 2 items on a 7-item Spinal Cord Injury Pain Instrument, SCIPI
• age of 18 - 65
• more than one-year post-injury
Exclusion Criteria:
• Not meeting injury type criteria
• Not meeting NP criteria
• Age 17 or less
• Less than a year following injury
• Inability to comprehend spoken English
• Prisoners
Other: VR Game 1, Other: VR Game 2
Spinal Cord Injuries, Neuropathic Pain
Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy (REVITALIZE 1)
Lynn Wilson - lwilson@fractyl.com
Sanyal, Arun, J
NCT04419779
HM20020776
Inclusion Criteria:
• Male, and non-pregnant, non-lactating females
• Age between 21 and 70 years (both inclusive)
• Subjects with T2D on stable dose (up to maximally approved doses) of metformin and up to 2 ADAs (including either GLP1 or DPP-4i and/or, TZD), requiring a minimum of 20 units up to a maximum of 60 units of basal insulin
• Glycosylated hemoglobin A1c (HbA1c) of 7.5-9.5% (both inclusive) confirmed at the end of at least 3 weeks stable run-in period
• FPG ≥180 to <270 mg/dL (measured after overnight 8-hour fasting and 24-36 hours after the last dose of glargine) at the end of at least 3 weeks stable run-in period
• Body Mass Index (BMI) ≥ 24 to ≤ 40 kg/m2
• Women of child-bearing potential (WOCBP) should have negative urine beta human chorionic gonadotropin (hCG) pregnancy test and must agree to use two of the established contraceptive methods throughout the study duration
• Able to sign an informed consent form and comply with study requirements.
Exclusion Criteria:
• Known case of absolute insulin deficiency as indicated by clinical assessment, and a fasting plasma C-peptide of <0.6 ng/ml
• Any drugs or concomitant medications (such as psychoactive drugs such as carbamazepine, phenobarbital, sympathomimetics (ephedrine etc.), corticosteroids, anabolic steroids, and male sex hormones such as testosterone, etc.) that can interfere with glucose metabolism
• Subjects who either are on SGLT2i, meglitinides, sulphonylurea (SUs), short or rapid acting insulin or any other class of ADA other than permitted baseline ADAs at the time of consent or who have a known or documented SGLT2i and/or metformin intolerance prior to the study
• Recurrent or severe urinary tract or genital mycotic infections or history of GU infection within 4 weeks prior to informed consent
• ALT >3 times upper limit normal values unless if associated with underlying NAFLD
• Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
• Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
• Ketosis-prone T2D
• History of non-healing diabetic ulcers or amputations
• History of more than 1 severe hypoglycemia episode or unawareness within past 6 months of screening
• In case of two or more glucose alert values of ≤70 mg/dL (3.9 mmol/L) unless a clear correctable precipitating factor can be identified/clinically significant hypoglycemia with self-monitored or laboratory plasma glucose level < 54 mg/dL (3.0 mmol/L / severe hypoglycemic episode requiring third party assistance occurring during run-in period
• Known intestinal autoimmune disease, as evidenced by either a positive anti-glutamic acid decarboxylase (GAD) test, including Celiac disease, or pre-existing symptoms of lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine
• Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone (TSH) value outside the normal range at screening)
• Known history of thyroid cancer or hyperthyroidism who have undergone treatment within past 12 months or inadequately controlled hyperthyroidism
• An uncontrolled endocrine condition such as multiple endocrine neoplasia etc. (except T2D)
• Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug-refractory esophageal reflux symptoms, active and uncontrolled Gastroesophageal Reflux Disease (GERD) (grade 3 esophagitis or greater)
• Known history of a structural or functional disorder of the stomach, including gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia or type II and higher paraoesophageal hernia) cancer or any other disorder of the stomach
• Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Billroth 2, Roux-en-Y gastric bypass, gastric sleeve or other similar procedures or conditions
• Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
• Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis; or hepatic decompensation/acute liver disease during the last 6 months; or alcoholic or autoimmune chronic hepatitis
• Symptomatic gallstones or symptomatic kidney stones, acute cholecystitis
• Clinically active systemic infection
• Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV), who are on potential immunosuppressants or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator
• History of active malignancy or partial remission from clinically significant malignancy within the past 5 years (except basal or squamous cell skin cancer or carcinoma in situ or those received curative treatment and in complete remission for 5 years or if subject confirmed as cancer free)
• Known active coagulopathy, or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
• Subjects with active helicobacter pylori infection (Subjects may be enrolled if they had history of h pylori infection and were successfully treated)
• Known cases of anemia, thalassemia or conditions that affect red blood cell (RBC) turnover such as recent blood transfusion within 90 days
• Use of anticoagulation therapy (such as warfarin, coumadin, novel oral anticoagulants [NOAC]) or anti-platelet agents (such as thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit
• Use of drugs known to affect GI motility (e.g., metoclopramide)
• History of moderate to severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 (estimated by Modification of Diet in Renal Disease [MDRD]) or end stage renal failure or on dialysis
• History of myocardial infarction, stroke, or major event requiring hospitalization within the last 3 months prior to screening
• History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
• Known case of severe peripheral vascular disease
• Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
• Clinically significant electrocardiogram (ECG) findings such as new clinically significant arrythmia or conduction disturbances that increases risk and requires intervention as determined by the investigator
• Subjects who are at risk for pancreatitis particularly those with a recent fasting triglycerides value of > 600 mg/dL value done within past 3 months
• Actively participating in a weight loss program and is currently not in the maintenance phase
• General contraindications to deep or conscious sedation or general anesthesia or high risk as determined by anesthesiologist (e.g., ASA score 4 or higher) or contraindications to upper GI Endoscopy
• History of any illicit alcohol or substance abuse
• Use of weight loss medication such as Meridia, Xenical, or over the counterweight loss medications or other prescribed medications used specifically for purpose of weight loss
• Use of Dietary supplements or herbal preparations that may have unknown effects on glycemic control, risk of bleeding
• Participating in another ongoing clinical trial of an investigational drug or device
• History of non-adherence to treatment in the previous 6 months, as determined by the investigator based on patient history, HbA1c value and/or drug accountability
• Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical trial participation
• Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
• Recovered from severe COVID-19 infection (requiring hospitalization) however still have persistent long COVID-19 symptoms (i.e., they have not recovered for several weeks or months since the start of symptoms that were suggestive of COVID-19, irrespective if they are tested or not).
Device: Duodenal Mucosal Resurfacing (DMR), Device: Duodenal Mucosal Resurfacing (Sham)
Type 2 Diabetes
Type 2 Diabetes, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Revita System, Duodenal Mucosal Resurfacing, Insulin-Dependent Diabetes Mellitus