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Back|NCT06001385Recruiting
Official Title

A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Phase
Phase 2
Sponsor
Center for International Blood and Marrow Transplant Research
Enrollment
313
Timeline
Dec 2023 → Jun 2026
About This Study

The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question\[s\] it aims to answer are: * Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant? * Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?

Eligibility Criteria

Inclusion Criteria

  • 1Age ≥ 18 years and \< 66 years (chemotherapy-based conditioning) or \< 61 years (total body irradiation \[TBI\]-based conditioning) at the time of signing informed consent
  • 2Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements.
  • 3Stated willingness to comply with all study procedures and availability for the duration of the study.
  • 4Planned MAC regimen as defined per study protocol
  • 5Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  • 6Product planned for infusion is MMUD T-cell replete PBSC allograft
  • 7HCT-CI \< 5. The presence of prior malignancy will not be used to calculate HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.
  • 8One of the following diagnoses:
  • 9Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extra-medullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • 10Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • 11Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results.
  • 12Estimated creatinine clearance ≥ 45mL/min calculated by equation.
  • 13Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin \> 50% and forced expiratory volume in first second (FEV1) predicted \> 50% based on most recent pulmonary function test (PFT) results
  • 14Liver function acceptable per local institutional guidelines
  • 15KPS of ≥ 70%
  • 16Age ≥18 years at the time of signing informed consent
  • 17Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
  • 18Stated willingness to comply with all study procedures and availability for the duration of the study.
  • 19Planned NMA/RIC regimen per study protocol
  • 20Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  • 21Product planned for infusion is MMUD T-cell replete PBSC allograft
  • 22One of the following diagnoses:
  • 23Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with \< 5% blasts in the bone marrow.
  • 24Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • 25Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • 26Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
  • 27Higher risk CMML according to CMML-specific prognostic scoring system or high risk MDS/MPN not otherwise specified are eligible, provided there is no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.
  • 28Patients with lymphoma with chemosensitive disease at the time of transplantation
  • 29Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  • 30Estimated creatinine clearance ≥ 45mL/min calculated by equation
  • 31Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results
  • 32Liver function acceptable per local institutional guidelines
  • 33KPS of ≥ 60%
  • 34Age ≥18 years at the time of signing informed consent
  • 35Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
  • 36Stated willingness to comply with all study procedures and availability for the duration of the study.
  • 37Planned NMA/RIC regimen per study protocol
  • 38Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
  • 39Product planned for infusion is MMUD T-cell replete PBSC allograft
  • 40Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.
  • 41Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
  • 42Estimated creatinine clearance ≥ 45 mL/min calculated by equation
  • 43Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results
  • 44Liver function acceptable per local institutional guidelines
  • 45KPS of ≥ 60%
  • 46Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or 7/8 (HLA-A, -B, -C, and -DRB1.
  • 47Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DQB1, and -DPB1.
  • 48Age ≥ 18 years and ≤ 40 years at the time of signing informed consent for PBSC donation. Note: donors are preferred to be ≤ 35.
  • 49Meet the donor registries' medical suitability requirements for PBSC donation.
  • 50Must undergo eligibility screening according to current Food and Drug Administration (FDA) requirements. Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need.
  • 51Must agree to donate PBSC.
  • 52Must have the ability to give informed consent according to standard (non-study) informed consent according to applicable donor regulatory requirements.

Exclusion Criteria

  • 1Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
  • 2Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • 3Subjects with a prior allogeneic transplant
  • 4Subjects with an autologous transplant within the past 3 months
  • 5Females who are breast-feeding or pregnant
  • 6Uncontrolled bacterial, viral, or fungal infection at the time of the transplant preparative regimen
  • 7Concurrent enrollment on a preventative GvHD and/or infectious disease prevention clinical trial.
  • 8Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant.
  • 9Patients who are HIV+ with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.
  • 10Donor unwilling or unable to donate.
  • 11Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, - DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.

Locations

32 sites participating in this study

Emory University

Atlanta, Georgia 30322

Recruiting

Joseph Rimando, MD

Mayo Clinic Arizona

Phoenix, Arizona 85054

Recruiting

Saurabh Chhabra, MD

Honor Health

Scottsdale, Arizona 85258

Recruiting

Adrienne Briggs, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →