Acute Lymphoblastic Leukemia (ALL) in Complete Remission, Acute Myeloid Leukemia (AML) in Remission
Conditions
Keywords
Sibling Donor Transplant, Allogeneic hematopoietic cell transplantation, GvHD Prophylaxis, Myeloablative regimen
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.
Interventions
Cyclophosphamide as GVHD prophylaxis will be on day +3 and day +5
DRUGMethotrexate
Methotrexate as GVHD prophylaxis will be on day +1, day +3, and day +6
Sponsors
King Faisal Specialist Hospital & Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Saudi Arabia
Contacts
Primary ContactRiad O El Fakih, MD
Outcome results
None listed