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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML) in Remission; Acute Lymphoblastic Leukemia (ALL) in Complete Remission
• Intervention / Treatment: Drug: Cyclophosphamide 50mg; Drug: Methotrexate

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 Type: Interventional
• Enrollment (Estimated): 264
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Riad O El Fakih, MD; Phone Number: 34760 + 966114647272; Email: relfakih1@kfshrc.edu.sa

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Recruiting
    • King Faisal Specialist Hospital & Research Center
    • Contact: Riad O El Fakih, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GRFS (GVHD-free/relapse-free survival)	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.	One-year post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Graft versus Host Disease (aGVHD)	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.	100 Day post transplant
Chronic Graft versus Host Disease (cGVHD)	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.	One year Post-transplant

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital & Research Center
• Investigators: Principal Investigator: Riad O El Fakih, MD, KFSH&RC; Principal Investigator: Mahmoud D Aljurf, MD, MPH, KFSH&RC; Principal Investigator: Marwan Y Shaheen, MD, KFSH&RC

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 17, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic hematopoietic cell transplantation; GvHD Prophylaxis; Sibling Donor Transplant; Myeloablative regimen
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cyclophosphamide; Methotrexate
• Other Study ID Numbers: 2181104; Saudi FDA (Other Identifier: 19052902)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No