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

Phase 3

Recruiting

• Conditions: Acute Lymphoblastic Leukemia (ALL) in Complete Remission; Acute Myeloid Leukemia (AML) in Remission
• Interventions: Drug: Cyclophosphamide 50mg; Drug: Methotrexate

• Registration Number: NCT04314219
• Lead Sponsor: King Faisal Specialist Hospital & Research Center

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2020-03-17
• Study First Submitted QC: 2020-03-17
• Study First Posted: 2020-03-19
• Study Start: 2021-08-15
• Status Verified: 2024-10
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-13
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 264

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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
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.
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.

Trial Locations

Locations (1)

King Faisal Specialist Hospital & Research Center; 🇸🇦 Riyadh, Saudi Arabia