Comparing Post-Transplant Cyclophosphamide As GVHD Prophylaxis to Standard of Care for Acute Leukemia Patients (PTCy-PMAT)

King Faisal Specialist Hospital & Research Center

Status and phase: Enrolling; Phase 3

Conditions: Acute Lymphoblastic Leukemia (ALL) in Complete Remission; Acute Myeloid Leukemia (AML) in Remission

Treatments: Drug: Methotrexate; Drug: Cyclophosphamide 50mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04314219

2181104

Saudi FDA (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 264 estimated patients

Sex: All

Ages: 14 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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264 participants in 2 patient groups

Arm 1: Intervention

Experimental group

Description:

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).

Treatment:

Drug: Cyclophosphamide 50mg

Arm 2: Standard of Care

Active Comparator group

Description:

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

Treatment:

Drug: Methotrexate