Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentClosed18 to 74NCINCI-2011-02053
CDR0000681025, CALGB 100801, U10CA180821, U10CA031946, NCT01168219

Trial Description


This phase II clinical trial is studying how well giving busulfan, fludarabine phosphate, and anti-thymocyte globulin followed by donor stem cell transplant and azacitidine works in treating patients with high-risk myelodysplastic syndrome and older patients with acute myeloid leukemia. Giving low doses of chemotherapy, such as busulfan and fludarabine phosphate, before a donor stem cell transplant 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-vs-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and giving azacitidine, tacrolimus, and methotrexate after the transplant may stop this from happening.

Further Study Information


I. To determine if this treatment can improve 2-year progression-free survival (PFS) in patients with high risk myelodysplastic syndrome (MDS) and in patients with acute myeloid leukemia (AML) >= 60 yrs age


I. To determine the safety and feasibility of using post-transplantation azacitidine.

II. To determine the ability to use pharmacokinetic-directed busulfan to achieve area under the curve (AUC) within 20% of target AUC in > 80% of patients.

III. To determine the rate of grade II-IV and III-IV acute graft-vs-host disease (GVHD).

IV. To determine the incidence of extensive chronic GVHD. V. To determine treatment-related mortality at 100 days and at 1 year. VI. To determine 5-year overall survival.


REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -7 to -3, busulfan IV over 45 minutes on days -6 to -3, and anti-thymocyte globulin IV over 4-10 hours on days -6 to -5 (matched sibling donor [MSD]) or -6 to -4 (matched unrelated donor [MUD]).

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0 or on days 0-1.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV on days -2 to 90 with taper on days 150-180. Patients also receive methotrexate IV on days 1, 3, 6 (MSD), and 11 (MUD).

CONSOLIDATION: Beginning on day 42, patients receive azacitidine subcutaneously (SC) or IV on days 1-5.

Treatment repeats every 4 weeks for 6 courses. Blood and bone marrow samples may be collected periodically for correlative and pharmacokinetic studies.

After completion of study treatment, patients are followed up every 6 months for 5 years.

Eligibility Criteria

Inclusion Criteria:

  • Meets one of the following sets of criteria:
  • Myelodysplastic syndromes (MDS):
  • Disease with high-risk features (found either at diagnosis or before initiation of cytotoxic therapy), defined as one of the following:
  • International prognostic scoring system (IPSS) risk >= intermediate-2
  • Refractory anemia with excess blasts by French-American-British (FAB) classification
  • High-risk cytogenetics (either complex or -7)
  • Less than 10% bone marrow blasts as determined by bone marrow biopsy within the past 4 weeks (reduction in marrow blast percentage may be achieved with chemotherapy or other therapy)
  • Less than 75 years old
  • Acute myeloid leukemia (AML):
  • No FAB M3
  • No acute leukemia following blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
  • Patients with preceding MDS or treatment-related AML are eligible
  • Prior central nervous system (CNS) involvement is allowed provided the disease is in remission at transplantation
  • Morphologic complete remission (leukemia-free state) is defined as meeting all of the following criteria:
  • Bone marrow blasts < 5% (as determined by bone marrow within the past 4 weeks), but without requirement for normal peripheral blood counts
  • No extramedullary leukemia
  • No blasts in peripheral blood
  • Achieved complete remission (CR) after no more than 2 courses of induction chemotherapy
  • Patients treated with azacitidine or decitabine who achieve a leukemia-free state are eligible (may have required up to 4 courses of therapy to reach this status)
  • Age 60 to 74 years
  • Donors must meet the following criteria:
  • One of the following:
  • HLA-identical sibling (6/6) by serologic typing for class (A, B) and low-resolution molecular typing for class II (DRB1)
  • Matched unrelated donor (8/8) by high-resolution molecular typing at HLA-A, -B, -C, and DRB1
  • No syngeneic donors
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Calculated creatinine clearance ≥ 40 mL/min
  • Bilirubin < 2 mg/dL OR bilirubin 2-3 mg/dL provided direct bilirubin is normal
  • Aspartate aminotransferase (AST) < 3 times upper limit of normal
  • Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
  • Left ventricle ejection fraction (LVEF) >= 30% by echocardiogram (ECHO) or multigated acquisition (MUGA)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled diabetes mellitus or active serious infections
  • No known hypersensitivity to E. coli-derived products, azacitidine, or mannitol
  • No human immunodeficiency virus (HIV) infection or active hepatitis B or C
  • Prior azacitidine or decitabine allowed
  • No patients who progressed from MDS to AML during treatment with azacitidine or decitabine
  • At least 4 weeks since prior deoxyribonucleic acid (DNA)-hypomethylating chemotherapy, radiotherapy, and/or surgery
  • No more than 2 courses of consolidation therapy before transplantation (for patients with AML)
  • Any consolidation regimen that does not require transplantation can be used
  • No more than 6 months from documentation of morphologic CR to transplantation

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Ravi Vij, Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01168219
    ClinicalTrials.gov processed this data on April 23, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.