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

Sponsor

King Faisal Specialist Hospital & Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04314219

Collaborator

(none)

264

Enrollment

Location

Arms

64.5

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia (ALL) in Partial Remission Acute Lymphoblastic Leukemia (ALL) in Complete Remission Acute Myeloid Leukemia (AML) in Remission	Drug: Cyclophosphamide 50mg Drug: Methotrexate	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Comparing Post-Transplant Cyclophosphamide With Calcineurin Inhibitors as A GVHD Prophylaxis to Standard Care of Methotrexate and Calcineurin Inhibitors for Acute Leukemia Incorporating Patient Pharmacogenomics Profiling

Actual Study Start Date :

Aug 15, 2021

Anticipated Primary Completion Date :

Jan 23, 2025

Anticipated Study Completion Date :

Dec 29, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: Cyclophosphamide 50mg Cyclophosphamide as GVHD prophylaxis will be on day +3 and day +5
Active Comparator: 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	Drug: Methotrexate Methotrexate as GVHD prophylaxis will be on day +1, day +3, and day +6

Arm

Intervention/Treatment

Experimental: 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).

Drug: Cyclophosphamide 50mg

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

Active Comparator: 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

Drug: Methotrexate

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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%2.
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.