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

Inclusion criteria

• 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)
• Males and Females Age ≥ 18 years.
• Weight of ≥ 35 Kg.
• Karnofsky performance status ≥ 70 %.
• Available mismatched related (haploidentical) or unrelated donors for peripheral blood stem cell (PBSC) donation.
• Subjects must otherwise fulfill institutional criteria for eligibility to undergo allogeneic stem cell transplantation.
• Absence of uncontrolled bacterial, viral or fungal infection at time of enrollment.
• Have adequate organ function.
• Subjects > 65-year-old receiving MAC conditioning will only be eligible if they have a HSCT-comorbidity index score < 5.
• Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits.

Exclusion criteria

• Prior allogeneic bone marrow, peripheral blood, or cord blood HSCT.
• Any subject with a history of significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support cardiac dysfunction.
• HIV positive.
• Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative.
• 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.
• 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.
• Subjects with a previous history of Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS) who are not good candidates for treatment with sirolimus.
• 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).
• Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results.