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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00015847
• Other study ID #: CDR0000068443
• Secondary ID: OHSU-6263OHSU-40
• Status: Terminated
• Phase: Phase 2
• First received: May 6, 2001
• Last updated: July 12, 2012
• Start date: April 2001
• Est. completion date: May 2011

Study information

• Verified date: June 2012
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Biological:
• recombinant interferon alfa
IFN-a 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.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Minor Cytogenetic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II	No
Primary	Complete Hematologic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II	No
Primary	Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)		At 6 and 12 months during phase II	No
Primary	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	Yes
Primary	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	No