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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Biological: recombinant interferon alfa; Drug: imatinib mesylate

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Cytogenetic Response at 6 and 12 Months (Phase II)	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%).	At 6 and 12 months during phase II
Minor Cytogenetic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II
Complete Hematologic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II
Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II
Treatment-related Toxicity (i.e., Grade 3 or 4 Nonhematologic Toxicity) as Measured by NCI CTCAE v3.0 (Phase I)	1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death	12 Months
Major Cytogenetic Response After 6 and 12 Months of Treatment.	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.	6 and 12 months after treatment

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Brian J. Druker, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Tyrosine Kinase Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiviral Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Interferons; Interferon-alpha
• Other Study ID Numbers: CDR0000068443; OHSU-6263 (Other Identifier: Old OHSU IRB); OHSU-409 (Other Identifier: OHSU IRB); NCI-2794; OHSU-HEM-00072-LX