Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Temporarily closed 60 to 74 NCI CALGB-100103 NCT00070135

Objectives

Primary

1. 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.

Secondary

1. 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.
2. 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.
3. Determine the pharmacokinetics of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• 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
  • 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 1,500/mm³*
    • Platelet count greater than 100,000/mm³*
    • 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

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

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

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior surgery

Patient Characteristics:

Age

• 60 to 74

Performance status

• 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• 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]

Renal

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

Cardiovascular

• LVEF at least 30% by MUGA or ECHO

Pulmonary

• DLCO greater than 40%
• No symptomatic pulmonary disease

Other

• 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

Expected Enrollment

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

Outcomes

Progression-free survival at 2 years

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.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Steven Devine, MD, Protocol chair		Ph: 614-293-2268 Email: steven.devine@osumc.edu

Registry Information
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
Trial Start Date		2004-01-15
Trial Completion Date		2005-04-16 (estimated)
Registered in ClinicalTrials.gov		NCT00070135
Date Submitted to PDQ		2003-08-14
Information Last Verified		2009-01-21
NCI Grant/Contract Number		CA31946

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