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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI OHSU-6263 NCI-2794, NCT00015847, 2794

Objectives

1. 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.)
2. Determine the safety and tolerability of this regimen in this patient population.
3. 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.
4. 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.
5. Determine the pharmacokinetics of this regimen in these patients.

Entry 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/mm³



• 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

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

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])

Expected Enrollment

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.

Outcomes

Treatment-related toxicity (i.e., grade 3 or 4 nonhematologic toxicity) as measured by NCI CTCAE v3.0 (Phase I)
Complete and major cytogenetic response at 6 and 12 months (Phase II)
Minor cytogenetic response at 6 and 12 months (Phase II)
Complete hematologic response at 6 and 12 months (Phase II)
Molecular response in patients with complete cytogenetic response at 6 and 12 months (Phase II)

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.

Trial Contact Information

Trial Lead Organizations

Oregon Health and Science University Cancer Institute

Brian Druker, MD, Protocol chair		Ph: 503-494-5596; 800-494-1234

Registry Information
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
Trial Start Date		2001-04-17
Registered in ClinicalTrials.gov		NCT00015847
Date Submitted to PDQ		2000-12-21
Information Last Verified		2005-08-11
NCI Grant/Contract Number		CA69533

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