Comparing Post-Transplant Cyclophosphamide as GVHD Prophylaxis to Standard of Care for Acute Leukemia Patients

Recruitment & Eligibility

Inclusion Criteria

Patients with Acute Leukemias (AML, ALL) in morphologic complete remission with or without hematologic recovery
Patients must have a fully matched (8/8) related donor willing to donate peripheral blood stem cells and must meet institutional criteria for donation
Planned Myeloablative conditioning regimen
Cardiac function: ejection fraction at rest ≥ 50% by MUGA or TTE
Estimated creatinine clearance greater than 50 mL/minute
Pulmonary function: DLCO ≥ 50% (adjusted for hemoglobin), and FVC and FEV1 ≥ 50%
Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and ALT/AST < 2.5x the upper normal limit
Signed informed consent

Exclusion Criteria

Karnofsky or Lansky Performance Score < 70%.
Active disease
Patients with uncontrolled bacterial, viral, or fungal infections
Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
Patients seropositive for HIV-1 or -2
Patients seropositive for HTLV-I or -II
Patients with active Hepatitis B or C viral replication by PCR
Women who are pregnant (positive serum or urine βHCG) or breastfeeding
Females with childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation
History of uncontrolled autoimmune disease or on active treatment
Patients with prior malignancies, except resected non-melanoma skin cancer or treated cervical carcinoma in situ; cancer treated with curative intent ≥ 5 years previously will be allowed; cancer treated with curative intent < 5 years previously will not be allowed.

Study & Design

Arm && Interventions

Group	Intervention	Description
Arm 1: Intervention	Cyclophosphamide 50mg	Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with cyclophosphamide, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV on Day +3 and Day +5 post stem cell infusion (only 2 doses).
Arm 2: Standard of Care	Methotrexate	Peripheral blood matched related donor HCT, using myeloablative conditioning regimen (IV Busulfan/IV Fludarabine for AML, IV VP16/TBI for ALL) HCT with methotrexate, and oral tacrolimus (or another calcineurin inhibitor if intolerant for tacrolimus) for GVHD prophylaxis

Primary Outcome Measures

Name	Time	Method
GRFS (GVHD-free/relapse-free survival)	One-year post-transplant	Defined as the non-occurrence of a grade 3-4 acute GVHD, or systemic therapy-requiring chronic GVHD, or relapse, or death during the first post-transplant year.

Secondary Outcome Measures

Name	Time	Method
Chronic Graft versus Host Disease (cGVHD)	One year Post-transplant	The cumulative incidence of systemic therapy-requiring chronic GVHD will be determined. Moderate and severe chronic GVHD will be defined per the NIH 2014 criteria.
Acute Graft versus Host Disease (aGVHD)	100 Day post transplant	The probabilities of grade II-IV and III-IV acute GVHD will be determined. Acute GVHD will be graded according to Glucksberg and NIH 2014 criteria.

Recruitment & Eligibility