Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML

Stanford University

Status and phase: Terminated; Phase 3

Conditions: Acute Myeloid Leukemia (AML); Leukemia; Leukemia, Myeloid

Treatments: Radiation: Total lymphoid irradiation (TLI); Procedure: Allogeneic HSCT; Drug: Cyclosporine (CSP); Drug: Mycophenolate mofetil (MMF); Drug: Anti-thymocyte globulin (ATG); Drug: Best standard care; Drug: Methylprednisolone sodium succinate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00568633

IRB-05567

BMT190 (Other Identifier)

97843 (Other Identifier)

Details and patient eligibility

About

Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.

Enrollment: 58 patients

Sex: All

Ages: 50 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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58 participants in 2 patient groups

Allo-HSCT + TLI + ATG

Experimental group

Description:

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

Treatment:

Drug: Methylprednisolone sodium succinate

Radiation: Total lymphoid irradiation (TLI)

Procedure: Allogeneic HSCT

Drug: Anti-thymocyte globulin (ATG)

Drug: Mycophenolate mofetil (MMF)

Drug: Cyclosporine (CSP)

Best Standard Care

Active Comparator group

Description:

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

Treatment:

Drug: Best standard care