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

NCT04314219 | Recruiting Phase 3 DMC

• 2 other identifiers: 2181104Saudi FDA
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Sibling Donor Transplant; Allogeneic hematopoietic cell transplantation; GvHD Prophylaxis; Myeloablative regimen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Acute Graft versus Host Disease (aGVHD)

  100 Day post transplant

• Chronic Graft versus Host Disease (cGVHD)

  One year Post-transplant

Study Arms (2)

Arm 1: Intervention

EXPERIMENTAL

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

Arm 2: Standard of Care

ACTIVE COMPARATOR

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

Interventions

Cyclophosphamide 50mg DRUG

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

Arm 1: Intervention

Methotrexate DRUG

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

Arm 2: Standard of Care

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• King Faisal Specialist Hospital & Research Center: lead

Study Sites (1)

King Faisal Specialist Hospital & Research Center

Riyadh, Saudi Arabia

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pathologic Complete Response; Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Riad O El Fakih, MD

  KFSH&RC

  PRINCIPAL INVESTIGATOR

• Mahmoud D Aljurf, MD, MPH

  KFSH&RC

  PRINCIPAL INVESTIGATOR

• Marwan Y Shaheen, MD

  KFSH&RC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Riad O El Fakih, MD

CONTACT

+ 966114647272; relfakih1@kfshrc.edu.sa

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 19, 2020
• Study Start: August 15, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 13, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)