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

OHSU Knight Cancer Institute

Status and phase

Terminated

Phase 2

Conditions

Leukemia

Treatments

Biological: recombinant interferon alfa

Drug: imatinib mesylate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00015847

OHSU-HEM-00072-LX

OHSU-6263 (Other Identifier)

OHSU-409 (Other Identifier)

CDR0000068443

NCI-2794

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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