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

NCT ID: NCT04314219

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 264 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-15
• Study Completion Date: 2026-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Arm 1: Intervention

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).

Group Type: EXPERIMENTAL

Cyclophosphamide 50mg

Intervention Type: DRUG

Cyclophosphamide as GVHD prophylaxis will be on day +3 and day +5

Arm 2: Standard of Care

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

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Methotrexate as GVHD prophylaxis will be on day +1, day +3, and day +6

Interventions

Cyclophosphamide 50mg

Cyclophosphamide as GVHD prophylaxis will be on day +3 and day +5

Intervention Type: DRUG

Methotrexate

Methotrexate as GVHD prophylaxis will be on day +1, day +3, and day +6

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Riad O El Fakih, MD

Role: PRINCIPAL_INVESTIGATOR

KFSH&RC

Mahmoud D Aljurf, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

KFSH&RC

Marwan Y Shaheen, MD

Role: PRINCIPAL_INVESTIGATOR

KFSH&RC

Locations

King Faisal Specialist Hospital & Research Center

Riyadh, , Saudi Arabia

Site Status: RECRUITING

Countries

Saudi Arabia

Central Contacts

Riad O El Fakih, MD

Role: CONTACT

relfakih1@kfshrc.edu.sa

+ 966114647272 ext. 34760

Facility Contacts

Riad O El Fakih, MD

Role: primary

Other Identifiers

Saudi FDA

Identifier Type: OTHER

Identifier Source: secondary_id

2181104

Identifier Type: -

Identifier Source: org_study_id