Imatinib Mesylate After a Donor Stem Cell Transplant in Treating Patients With Philadelphia Chromosome-Positive Leukemia

A Multicenter Pilot Study Evaluating the Safety and Efficacy of Imatinib as Post-Transplant Therapy for High- Risk Philadelphia Chromosome-Positive Leukemias

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving imatinib mesylate after a donor stem cell transplant may prevent the recurrence of Philadelphia chromosome-positive leukemia.

PURPOSE: This phase I/II trial is studying the side effects of giving imatinib mesylate after a donor stem cell transplant and to see how well it works in treating patients with Philadelphia chromosome-positive leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Procedure: adjuvant therapy; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

Primary

• Determine the safety of adjuvant imatinib mesylate after allogeneic hematopoietic stem cell transplantation (AHSCT) in patients with high-risk Philadelphia chromosome-positive leukemia.

Secondary

• Determine the bcr/abl transcript load during the first 90 days after AHSCT in patients treated with this drug from the time of engraftment.
• Determine the 1-year survival of patients treated with this drug.

OUTLINE: This is an open-label, pilot, multicenter study.

Beginning within 14-30 days after allogeneic stem cell transplantation, patients receive oral imatinib mesylate once daily until 1 year after transplantation. Treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Acute lymphoblastic leukemia or chronic myeloid leukemia (CML) characterized by p^190 and/or p^210 bcr/abl gene rearrangement
  • Accelerated or blastic phase CML
  • CML in second or greater chronic phase
• No imatinib mesylate-resistant leukemia

• Planned allogeneic hematopoietic stem cell transplantation

  • Availability of an appropriately matched related or unrelated donor
  • Autologous or nonmyeloablative transplantation is not allowed

• None of the following within 4 days after the date of neutrophil engraftment*:

  • More than 5% marrow blasts
  • Circulating peripheral blood leukemic blasts
  • Aberrant antigen expression on marrow myeloblasts ≥ 1% by multidimensional flow cytometric assay
  • Presence of bcr/abl in > 5% of marrow interphase nuclei by fluorescent in situ hybridization
  • More than 1 of 20 Philadelphia chromosome-positive marrow metaphases
  • CNS involvement by leukemia NOTE: *The date of neutrophil engraftment is defined as the second consecutive day at which the peripheral blood absolute neutrophil count exceeds 500/mm3

PATIENT CHARACTERISTICS:

Performance status

• Not specified

Life expectancy

• At least 2 months

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count ≥ 1,200/mm^3 (use of filgrastim [G-CSF] allowed)

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known imatinib mesylate hypersensitivity
• No other disease that severely limits life expectancy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety at 90 days following transplant

Secondary Outcome Measures

Outcome Measure
Survival at 1 year
BCR/ABL transcript load at 90 days following transplant
Standard management of progressive minimal residual disease at 90 days following transplant

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Investigators: Study Chair: Paul Carpenter, MD, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 27, 2005

Study Record Updates

• Last Update Posted (Estimate): November 30, 2011
• Last Update Submitted That Met QC Criteria: November 28, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: childhood acute lymphoblastic leukemia in remission; chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Chromosome Aberrations; Translocation, Genetic; Leukemia; Philadelphia Chromosome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: 1867.00; FHCRC-1867.00; CDR0000355118 (Registry Identifier: PDQ)