Donor Stem Cell Transplant in Treating Young Patients With Acute Myeloid Leukemia With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory or Relapsed Acute Myelogenous Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monosomy
Intervention: anti-thymocyte globulin; busulfan; cyclophosphamide; cyclosporine; methotrexate; methylprednisolone; tacrolimus; laboratory biomarker analysis; pharmacological study; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation
Intervention description: Given IV; Given IV; Given IV; Given IV or orally; Given IV; Given IV; Given IV; Correlative studies; Correlative studies; allogeneic bone marrow transplantation; Undergo allogeneic hematopoietic SCT
Intervention MeSH terms: Cyclosporine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Busulfan; Methotrexate; Tacrolimus; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 158.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No
Keywords: recurrent childhood acute myeloid leukemia; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that
      closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops
      the patient's immune system from rejecting the donor's stem cells. The donated stem cells may
      replace the patient's immune cells and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an
      immune response against the body's normal cells. Giving antithymocyte globulin before
      transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may
      stop this from happening.

      PURPOSE: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting
      leukemia. Bone marrow donors can be selected based on the type of NK cells they have,
      specifically the killer immunoglobulin receptor (KIR) type. This study provides information
      on KIR type from potential donors, which can be used in selecting the bone marrow donor. This
      phase II trial of unrelated donor stem cell transplant in patients with high risk AML
      (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of
      the patients and potential donors will be available to the treating transplant physician at
      the time of donor selection.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of one of the following:

               -  Patients with primary refractory acute myeloid leukemia (AML), defined as ≥ 5%
                  bone marrow blasts after two induction courses of chemotherapy

               -  Primary refractory AML, defined as ≥ 5% bone marrow blasts after two induction
                  courses of chemotherapy

               -  AML or myelodysplastic syndrome with -5/5q- or monosomy 7 without
                  inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBPα mutations

               -  Relapsed AML (≥ 5% bone marrow blasts) who meet the customary WHO criteria for
                  AML

               -  AML and high FLT3 internal tandem duplication allelic ratio (high FLT3-ITD AR),
                  defined as > 0.4

               -  All cases of therapy-related AML (therapy-related AML is considered high risk)

               -  Patients with AML, without inv(16)/t(16;16) or t(8;21), monosomy 7, -5/5q-, NPM,
                  or CEPBα mutations, or high FLT3-ITD AR, but with evidence of residual AML (≥
                  0.1%) at the end of Induction I; or if a minimal residual disease (MRD) is not
                  performed, then with > 15% bone marrow blasts by morphology after one induction
                  course of chemotherapy

                    -  Any flow-based MRD is eligible for AAML05P1 for patients not on AAML1031,
                       whereas patients on AAML1031 must utilize the central lab as per the
                       AAML1031 protocol guidelines

          -  No Fanconi anemia

          -  Recipients of unrelated marrow or cord blood are eligible for this study

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) (for patients over 16 years of age) or Lansky PS
             (for patients 16 and under) 50-100%

          -  Total bilirubin ≤ 2 mg/dL

          -  SGOT (AST) or SGPT (ALT) ≤ 2.5 times upper limit of normal

          -  DLCO ≥ 50% OR a normal chest x-ray and pulse oximetry in patients who are unable to
             undergo pulmonary function tests

          -  Shortening fraction ≥ 27% by ECHO

          -  Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min OR
             creatinine adjusted according to age

          -  HIV negative

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Patients with proven or suspected bacterial sepsis, pneumonia, or meningitis are
             eligible provided appropriate therapeutic measures have been initiated to control the
             presumed or proven infection, and systemic signs are not life-threatening

          -  No evidence or presence of a fungal infection within the past 30 days

        PRIOR CONCURRENT THERAPY:

          -  Prior chemotherapy, radiotherapy or any antileukemic therapy allowed provided patients
             meet 1 of the following criteria:

               -  Received initial treatment for relapsed AML

               -  Patients with primary induction failure or relapse who have already received
                  initial therapy and who may have gone on to have additional therapy prior to
                  receiving protocol stipulated therapy on AAML05P1

          -  No treatment for fungal infection within the past 30 days

          -  Concurrent radiotherapy to localized painful lesions allowed

          -  No other concurrent cancer chemotherapy or immunomodulating agents