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

Primary Purpose

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

Status

Recruiting

Phase

Phase 3

Locations

Saudi Arabia

Study Type

Interventional

Intervention

Cyclophosphamide 50mg

Methotrexate

About this trial

This is an interventional prevention trial for Acute Lymphoblastic Leukemia (ALL) in Complete Remission focused on measuring Sibling Donor Transplant, Allogeneic hematopoietic cell transplantation, GvHD Prophylaxis, Myeloablative regimen

Eligibility Criteria

14 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

King Faisal Specialist Hospital & Research CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1: Intervention

Arm 2: Standard of Care

Arm Description

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).

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT04314219

First Posted

March 17, 2020

Last Updated

October 3, 2023

Sponsor

King Faisal Specialist Hospital & Research Center

1. Study Identification

Unique Protocol Identification Number

NCT04314219

Brief Title

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

Acronym

PTCy-PMAT

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 15, 2021 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

King Faisal Specialist Hospital & Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

264 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: Intervention

Arm Type

Experimental

Arm Description

Arm Title

Arm 2: Standard of Care

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide 50mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

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

Primary Outcome Measure Information:

Title

GRFS (GVHD-free/relapse-free survival)

Description

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.

Time Frame

One-year post-transplant

Secondary Outcome Measure Information:

Title

Acute Graft versus Host Disease (aGVHD)

Description

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.

Time Frame

100 Day post transplant

Title

Chronic Graft versus Host Disease (cGVHD)

Description

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.

Time Frame

One year Post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Riad O El Fakih, MD

Phone

+ 966114647272

Ext

34760

relfakih1@kfshrc.edu.sa

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Riad O El Fakih, MD

Organizational Affiliation

KFSH&RC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mahmoud D Aljurf, MD, MPH

Organizational Affiliation

KFSH&RC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Marwan Y Shaheen, MD

Organizational Affiliation

KFSH&RC

Official's Role

Principal Investigator

Facility Information:

Facility Name

King Faisal Specialist Hospital & Research Center

City

Riyadh

Country

Saudi Arabia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Riad O El Fakih, MD

12. IPD Sharing Statement

Learn more about this trial

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

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