Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
Condition: Leukemia, Myeloid; Leukemia; Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Allogeneic HSCT; Anti-thymocyte globulin (ATG); Cyclosporine (CSP); Mycophenolate mofetil (MMF); Total lymphoid irradiation (TLI); Methylprednisolone sodium succinate; Best standard care
Intervention description: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg.; 1.5 mg/kg for 5 days by IV; 6.25 mg/kg twice daily oral; 15 mg/kg twice daily oral; 80 cGy/fraction radiotherapy in 10 fractions.; 1.0 mg/kg for 5 days by IV; Intervention consist of:
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
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Treatment assignment was based on availability of an HLA-matched donor.
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 50 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

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