Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia

This study has been terminated.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00015847
First received: May 6, 2001
Last updated: July 12, 2012
Last verified: June 2012
  Purpose

RATIONALE: Imatinib mesylate and interferon alfa may interfere with the growth of the cancer cells. Combining imatinib mesylate with interferon alfa may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with interferon alfa in treating patients who have chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Biological: recombinant interferon alfa
Drug: imatinib mesylate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Complete Cytogenetic Response at 6 and 12 Months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]

    Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:

    Complete* (0% Ph-positive cells) Partial* (1-34%) Minor (35-95%) None (96-100%).


  • Minor Cytogenetic Response at 6 and 12 Months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  • Complete Hematologic Response at 6 and 12 Months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  • Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II) [ Time Frame: At 6 and 12 months during phase II ] [ Designated as safety issue: No ]
  • Treatment-related Toxicity (i.e., Grade 3 or 4 Nonhematologic Toxicity) as Measured by NCI CTCAE v3.0 (Phase I) [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death

  • Major Cytogenetic Response After 6 and 12 Months of Treatment. [ Time Frame: 6 and 12 months after treatment ] [ Designated as safety issue: No ]

    Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:

    Complete* (0% Ph-positive cells) Partial* (1-34%) Minor (35-95%) None (96-100%).

    *Major cytogenetic response includes complete and partial cytogenetic response.



Enrollment: 25
Study Start Date: April 2001
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: recombinant interferon alfa
    IFN-α will be given at a dose ranging up to 5 MIU daily via subcutaneous injection.
    Drug: imatinib mesylate
    Once daily oral administration of STI571 (imatinib mesylate) at a dose of 400 mg or 600mg for 12 months.
    Other Name: STI571
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of interferon alfa administered with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)
  • Determine the safety and tolerability of this regimen in this patient population.
  • Determine the complete, major, and minor cytogenetic response rates and complete hematologic response rate in patients after 6 and 12 months of treatment with this regimen.
  • Determine the molecular response (reverse transcriptase-polymerase chain reaction for bcr-abl) rate in patients who have a complete cytogenetic response after 6 and 12 months of treatment with this regimen.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

  • Phase I (closed to accrual as of 7/9/03): Patients receive oral imatinib mesylate once daily beginning on day 1 and interferon alfa (IFN-A) subcutaneously once daily or 3 times weekly beginning on day 14. Courses repeat every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of 1 year of therapy, patients may receive additional therapy, provided that the patient is benefiting from imatinib mesylate. IFN-A is discontinued in patients who achieve a molecular remission that is confirmed on 2 successive bone marrow samples. Imatinib mesylate is discontinued in patients who achieve and maintain a molecular remission for 2 years.

Sequential dose escalation of IFN-A is followed by sequential dose escalation of imatinib mesylate. Cohorts of 3-6 patients receive escalating doses of IFN-A and then imatinib mesylate until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for the phase I portion of this study. (Phase I closed to accrual as of 7/9/03.) A total of 40 patients will be accrued for the phase II portion of the study within 3-4 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Cytogenetically confirmed chronic myelogenous leukemia (CML)

    • Less than 15% blasts in peripheral blood or bone marrow
    • Less than 30% blasts and promyelocytes in peripheral blood or bone marrow
    • Less than 20% basophils in blood or bone marrow
    • Platelet count at least 100,000/mm^3
  • No leukemia beyond bone marrow, blood, liver, or spleen
  • No chloroma
  • Phase I (closed to accrual as of 7/9/03):

    • Philadelphia (Ph) chromosome-positive CML in chronic phase
  • Phase II:

    • Newly diagnosed Ph chromosome-positive CML in chronic phase
    • Initial diagnosis within 6 months of study
    • No prior therapy for CML except hydroxyurea and/or anagrelide hydrochloride
  • Phase I (closed to accrual as of 7/9/03) and II:

    • No identified sibling donors where allogeneic stem cell transplantation is elected as first-line therapy

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST or ALT no greater than 2 times ULN

Renal:

  • Creatinine no greater than 1.5 times ULN

Cardiovascular:

  • No New York Heart Association class III or IV heart disease

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective barrier contraception during and for at least 3 months after study participation
  • No other serious uncontrolled medical condition
  • No autoimmune disease
  • No prior noncompliance to medical regimens or potential unreliability
  • No prior grade 3 or greater non-hematologic toxicity due to prior interferon (phase I [closed to accrual as of 7/9/03])

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • No prior bone marrow or peripheral blood stem cell transplantation
  • At least 2 weeks since prior interferon alfa (phase I [closed to accrual as of 7/9/03])

Chemotherapy:

  • See Disease Characteristics
  • At least 6 weeks since prior busulfan (phase I [closed to accrual as of 7/9/03] )
  • At least 2 weeks since prior cytarabine (phase I [closed to accrual as of 7/9/03])
  • No concurrent chemotherapy
  • Concurrent hydroxyurea allowed during the first 3 months of study

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • At least 4 weeks since prior investigational agents other than imatinib mesylate (phase I [closed to accrual as of 7/9/03])
  • No concurrent grapefruit juice
  • Concurrent anagrelide hydrochloride allowed during the first 3 months of study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00015847

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Study Chair: Brian J. Druker, MD OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00015847     History of Changes
Other Study ID Numbers: CDR0000068443, OHSU-6263, OHSU-409, NCI-2794, OHSU-HEM-00072-LX
Study First Received: May 6, 2001
Results First Received: June 6, 2012
Last Updated: July 12, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Interferon-alpha
Interferon Alfa-2a
Interferons
Imatinib
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014