Clinical trial NCT04314219: Comparing Post-Transplant Cyclophosphamide As GVHD Prophylaxis to Standard of Care for Acute Leukemia Patients
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
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
First posted: 2020-03-19
Enrollment: 264
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: GRFS (GVHD-free/relapse-free survival)
timeFrame: One-year post-transplant
Secondary outcomes:
measure: Acute Graft versus Host Disease (aGVHD)
timeFrame: 100 Day post transplant
measure: Chronic Graft versus Host Disease (cGVHD)
timeFrame: One year Post-transplant
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
Study officials:
affiliation: KFSH&RC
name: Riad O El Fakih, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KFSH&RC
name: Mahmoud D Aljurf, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: KFSH&RC
name: Marwan Y Shaheen, MD
role: PRINCIPAL_INVESTIGATOR
References: