Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: October 3, 2003
Last updated: September 6, 2012
Last verified: December 2011

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood 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 system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with busulfan followed by a donor stem cell transplant works in treating older patients with acute myeloid leukemia that is in the first complete remission.

Condition Intervention Phase
Biological: filgrastim
Biological: graft-versus-tumor induction therapy
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: January 2004
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Detailed Description:



  • Determine whether allogeneic stem cell transplantation from a matched sibling or unrelated donor using a nonmyeloablative preparative regimen comprising fludarabine and busulfan results in a 2-year disease-free survival that is better than historical results using standard chemotherapy in older patients with acute myeloid leukemia in first morphologic complete remission.


  • Determine the 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host disease, and relapse in patients treated with this regimen.
  • Determine the recovery of T- and B-cell number and function and the time course of T, B, and myeloid progenitor chimerism in patients treated with this regimen.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive oral or IV tacrolimus twice daily starting on days -2, with tapering between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6,and 11 and rabbit antithymocyte globulin (Thymoglobulin) IV over 4-6 hours on days -4 through -2.
  • Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo allogeneic PBSC transplantation on day 0. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 12 and continuing until blood counts recover. Patients with progressive disease will be removed from the study and may receive additional treatment at the discretion of the investigator.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.


Ages Eligible for Study:   60 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of acute myeloid leukemia (AML) in first morphologic complete remission

    • No FAB M3 disease
    • Preceding myelodysplastic syndromes and treatment-related AML allowed
  • Morphologic complete remission achieved within the past 6 months and after no more than 2 courses of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than 4 courses of a hypomethylating agent-containing regimen including either 5-azacytidine or decitabine

    • Complete morphologic remission is defined by all of the following criteria:

      • Normal bone marrow morphology with less than 5% blasts
      • Absolute neutrophil count greater than 1,000/mm^3*
      • Platelet count greater than 100,000/mm^3*
      • No extramedullary leukemia
      • No blasts in peripheral blood NOTE: *Must be sustained for at least 30 days
  • No more than 2 courses of prior consolidation therapy

    • Any consolidation regimen that does not require transplantation allowed
  • No acute leukemia after blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
  • Prior CNS involvement allowed provided the disease is in remission at time of transplantation
  • The following donors will be allowed:

    • Available HLA-identical (6/6) sibling donor by serological typing (A, B, DR)
    • Locus matched unrelated donor (10/10) by high resolution molecular typing (HLA-A, -B, -C, -DRB1, and -DQB1).
    • No syngeneic donors



  • 60 to 74

Performance status

  • 0-2

Life expectancy

  • Not specified


  • See Disease Characteristics


  • Bilirubin less than 2 mg/dL*

    • Bilirubin 2-3 mg/dL with normal direct bilirubin allowed
  • AST less than 3 times upper limit of normal* NOTE: *Unless attributable to disease


  • Creatinine clearance at least 40 mL/min (unless attributable to disease)


  • LVEF at least 30% by MUGA or ECHO


  • DLCO greater than 40%
  • No symptomatic pulmonary disease


  • Not pregnant
  • Fertile patients must use effective contraception
  • HIV negative
  • No uncontrolled diabetes mellitus
  • No active serious infection requiring antibiotics
  • No known hypersensitivity to E. coli-derived products


Biologic therapy

  • See Disease Characteristics


  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy

Endocrine therapy

  • Not specified


  • At least 4 weeks since prior radiotherapy


  • At least 4 weeks since prior surgery
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00070135

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States, 02115
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, United States, 11042
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Mount Sinai Medical Center
New York, New York, United States, 10029
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Cancer and Leukemia Group B
Study Chair: Steven M. Devine, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00070135     History of Changes
Other Study ID Numbers: CDR0000330001, CALGB-100103
Study First Received: October 3, 2003
Last Updated: September 6, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia in remission
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Fludarabine phosphate
Alkylating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015