A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Prior treatment

• Subjects with a prior allogeneic transplant
• Subjects with an autologous transplant within the past 3 months
• Concurrent enrollment on a GVHD prevention clinical trial
• Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant

Other illness

• Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
• Patients who are HIV-positive 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.

Other

• Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
• Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
• Subjects who are breastfeeding or pregnant

• Age 18 to \< 66 years (chemotherapy-based conditioning) or \< 61 years (TBI-based conditioning) at the time of signing informed consent
• Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Planned MAC regimen (see Table 8 in Section 7.4 for allowed MAC regimens)
• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age 16-35
• Product planned for infusion is MMUD T-cell replete PBSC as allograft
• HCT-CI \< 5 (Appendix H - Hematopoietic Cell Transplant Comorbidity Index Scoring). 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.
• One of the following diagnoses:
  • AML, ALL, or other acute leukemia in first remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extramedullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • Patients 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% vs 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
• Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results
• Estimated creatinine clearance ≥ 45mL/min calculated by equation
• Pulmonary 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 PFT results
• Liver function acceptable per local institutional guidelines
• KPS of ≥ 70% (Appendix I - Performance Status)
• Age ≥ 18 years at the time of signing informed consent
• Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Planned NMA/RIC regimen (see
• Table 9 in Section 7.4 for allowed NMA/RIC regimens)
• Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age 16-35
• Product planned for infusion is MMUD T-cell replete PBSC allograft
• One of the following diagnoses:
  • Patients 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. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • Patients 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% vs 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
  • Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation.
  • Higher-risk chronic myelomonocytic leukemia (CMML) according to CMML-specific prognostic scoring system or high-risk MDS/myeloproliferative neoplasms (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.
  • Patients with lymphoma with chemosensitive disease at the time of transplantation.
  • Patients with primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia, polycythemia vera or MDS with grade 4 fibrosis.
• Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
• Estimated creatinine clearance ≥ 45mL/min calculated by equation
• Pulmonary function: DLCO corrected for hemoglobin ≥ 50% and FEV1 predicted ≥ 50% based on most recent PFT results
• Liver function acceptable per local institutional guidelines
• KPS of ≥ 60% (Appendix I - Performance Status)