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

Inclusion Criteria, MAC RECIPIENTS:

1. Age 18 to < 66 years (chemotherapy-based conditioning) or < 61 years (TBI-basedconditioning) at the time of signing informed consent

2. Patient or legally authorized representative has the ability to provide informedconsent according to the applicable regulatory and institutional requirements

3. Stated willingness to comply with all study procedures and availability for theduration of the study

4. Planned MAC regimen (see Table 8 in Section 7.4 for allowed MAC regimens)

5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) withage 16-35

6. Product planned for infusion is MMUD T-cell replete PBSC as allograft

7. 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 thistrial, to allow for the inclusion of patients with secondary or therapy-related AMLor MDS.

8. One of the following diagnoses:

9. AML, ALL, or other acute leukemia in first remission or beyond with ≤ 5% marrowblasts and no circulating blasts or evidence of extramedullary disease.Documentation of bone marrow assessment will be accepted within 45 days priorto the anticipated start of conditioning.

10. Patients with MDS with no circulating blasts and with < 10% blasts in the bonemarrow (higher blast percentage allowed in MDS due to lack of differences inoutcomes with < 5% vs 5-10% blasts in MDS). Documentation of bone marrowassessment will be accepted within 45 days prior to the anticipated start ofconditioning.

11. Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recentechocardiogram or multi-gated acquisition scan (MUGA) results

12. Estimated creatinine clearance ≥ 45mL/min calculated by equation

13. 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

14. Liver function acceptable per local institutional guidelines

15. KPS of ≥ 70% (Appendix I - Performance Status)

Inclusion Criteria, RIC/NMA RECIPIENTS:

1. Age ≥ 18 years at the time of signing informed consent

2. Patient or legally authorized representative has the ability to provide informedconsent according to the applicable regulatory and local institutional requirements

3. Stated willingness to comply with all study procedures and availability for theduration of the study

4. Planned NMA/RIC regimen (see

5. Table 9 in Section 7.4 for allowed NMA/RIC regimens)

6. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) withage 16-35

7. Product planned for infusion is MMUD T-cell replete PBSC allograft

8. One of the following diagnoses:

9. Patients with acute leukemia or chronic myeloid leukemia (CML) with nocirculating blasts, no evidence of extramedullary disease, and with < 5% blastsin the bone marrow. Documentation of bone marrow assessment will be acceptedwithin 45 days prior to the anticipated start of conditioning.

10. Patients with MDS with no circulating blasts and with < 10% blasts in the bonemarrow (higher blast percentage allowed in MDS due to lack of differences inoutcomes with < 5% vs 5-10% blasts in MDS.) Documentation of bone marrowassessment will be accepted within 45 days prior to the anticipated start ofconditioning.

11. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (includingprolymphocytic leukemia) with chemosensitive disease at time oftransplantation.

12. Higher-risk chronic myelomonocytic leukemia (CMML) according to CMML-specificprognostic scoring system or high-risk MDS/myeloproliferative neoplasms (MPN)not otherwise specified are eligible, provided there is no evidence ofhigh-grade bone marrow fibrosis or massive splenomegaly at the time ofenrollment.

13. Patients with lymphoma with chemosensitive disease at the time oftransplantation.

14. Patients with primary myelofibrosis or myelofibrosis secondary to essentialthrombocythemia, polycythemia vera or MDS with grade 4 fibrosis.

15. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recentechocardiogram or MUGA results with no clinical evidence of heart failure

16. Estimated creatinine clearance ≥ 45mL/min calculated by equation

17. Pulmonary function: DLCO corrected for hemoglobin ≥ 50% and FEV1 predicted ≥ 50%based on most recent PFT results

18. Liver function acceptable per local institutional guidelines

19. KPS of ≥ 60% (Appendix I - Performance Status)

Exclusion Criteria:

1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donoravailable

2. Subject unwilling or unable to give informed consent, or unable to comply with theprotocol including required follow-up and testing

3. Subjects with a prior allogeneic transplant

4. Subjects with an autologous transplant within the past 3 months

5. Subjects who are breastfeeding or pregnant

6. Uncontrolled bacterial, viral or fungal infection at the time of the transplantpreparative regimen

7. Concurrent enrollment on a GVHD prevention clinical trial

8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels priorto transplant

9. Patients who are HIV-positive with persistently positive viral load. HIV-infectedpatients on effective anti-retroviral therapy (ART) with undetectable viral loadwithin 6 months are eligible for this trial. Patients with well-controlled HIV areeligible provided resistance panels are negative, the patient is compliant with ART,and their disease remains well controlled.