Prevention of GvHD in Participants With Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplant (HSCT)

Eligibility Criteria

• 1. Subjects with one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (B- or T-ALL), Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), or Chronic myelomonocytic leukemia (CMML)
• 2. Males and Females Age ≥ 18 years.
• 3. Weight of ≥ 35 Kg.
• 4. Karnofsky performance status ≥ 70 %.
• 5. Available mismatched related (haploidentical) or unrelated donors for peripheral blood stem cell (PBSC) donation.
• 6. Subjects must otherwise fulfill institutional criteria for eligibility to undergo allogeneic stem cell transplantation.
• 7. Absence of uncontrolled bacterial, viral or fungal infection at time of enrollment.
• 8. Have adequate organ function.
• 9. Subjects \> 65-year-old receiving MAC conditioning will only be eligible if they have a HSCT-comorbidity index score \< 5.
• 10. Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits.
• 1. Prior allogeneic bone marrow, peripheral blood, or cord blood HSCT.
• 2. Any subject with a history of significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support cardiac dysfunction.
• 3. HIV positive.
• 4. Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative.
• 5. Positive hepatitis-C antibody with positive Recombinant Immunoblot Assay (RIBA) or PCR unless the subject has received curative anti-viral treatment and confirmed negative viral load by PCR.
• 6. Received another investigational agent for treatment of disease understudy within 28 days (or 5 half-lives, whichever is shorter) of conditioning and/or have not recovered from treatment related toxicities.
• 7. Subjects with a previous history of Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS) who are not good candidates for treatment with sirolimus.
• 8. Subjects that are pregnant, breast feeding or aim to become pregnant during the study period. (Subjects must agree to use a highly effective method of contraception).
• 9. Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results.