Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
Leukemia, Myeloid, Leukemia, Acute Myeloid Leukemia (AML)
About this trial
This is an interventional treatment trial for Leukemia, Myeloid
Eligibility Criteria
INCLUSION CRITERIA
- ≥ 50 years of age and ≤ 75 years of age.
- De novo acute myelogenous leukemia (AML), based on FAB and WHO criteria.
- Intermediate or unfavorable cytogenetic abnormalities based on Southwest Oncology Group (SWOG) Cytogenetic Criteria.
- First morphologic complete remission (CR), or CRp (a complete remission but with low platelets) following 1 or 2 courses of induction therapy, documented no more than 8 weeks prior to the date of enrollment and confirmed at time of enrollment.
- Karnofsky Performance Score ≥ 60.
- Suitable for non-myeloablative transplantation or best treatment.
- Able to understand and willing to sign a written informed consent document.
EXCLUSION CRITERIA
- AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria
- AML, either treatment-related or MDS-related
- Active CNS disease as identified by positive CSF cytospin at time of enrollment.
- Prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. (EXCEPTION: Cancer treated with curative intent > 5 years previously is allowed. EXCEPTION: Low grade lymphoma is allowed as long as active treatment is not required for control of disease)
- Planned for allogeneic transplant using a full-dose conditioning
- Life expectancy < 1 year due to diseases other than malignancy
- Pregnant or breastfeeding.
- HIV-seropositive.
- Uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month.
- Symptomatic coronary artery disease or uncontrolled congestive heart failure. Left ventricular ejection fraction (LVEF) is not required to be measured, however if measured, exclusion if ejection fraction is < 30%.
- Requiring supplementary continuous oxygen. Diffusing capacity of the lungs for carbon monoxide (DLCO) is not required to be measured, however if it is measured, exclusion if DLCO < 35%.
- Fulminant liver failure
- Cirrhosis with evidence of portal hypertension or bridging fibrosis
- Alcoholic hepatitis
- Esophageal varices
- A history of bleeding esophageal varices
- Hepatic encephalopathy
- Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
- Ascites related to portal hypertension
- Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
- Symptomatic biliary disease
Sites / Locations
- Kaiser Permanente Northern California
- Cedars-Sinai Medical Center
- Univeristy of California Davis Medical Center
- Stanford University School of Medicine
- West Virginia University Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Allo-HSCT + TLI + ATG
Best Standard Care
Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28
Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation