Overview
This randomized clinical trial will evaluate two approaches of GvHD prophylaxis; the standard of care GVHD prophylaxis regimen (methotrexate/calcineurin inhibitors) and post-transplant cyclophosphamide with calcineurin inhibitors for their efficacy as a new GVHD prophylaxis strategy.
Description
An open-label randomized clinical trial will be performed. Eligible patients are females and males, between 14 and 65 years undergoing allo-HCT for treatment of Acute Leukemia (AML or ALL). Patients must have a matching related peripheral blood stem cell donor. Patients from or referred to the KFSH&RC for allogeneic transplant consideration will be offered the opportunity to participate in this trial.
Treatment Description:
Patients will be randomized on one of the arms; an intervention or a standard of care arm.
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.