Clinical trial NCT00015847: Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Complete Cytogenetic Response at 6 and 12 Months (Phase II)
timeFrame: At 6 and 12 months during phase II
measure: Minor Cytogenetic Response at 6 and 12 Months (Phase II)
timeFrame: At 6 and 12 months during phase II
measure: Complete Hematologic Response at 6 and 12 Months (Phase II)
timeFrame: At 6 and 12 months during phase II
measure: Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)
timeFrame: At 6 and 12 months during phase II
measure: Treatment-related Toxicity (i.e., Grade 3 or 4 Nonhematologic Toxicity) as Measured by NCI CTCAE v3.0 (Phase I)
timeFrame: 12 Months
measure: Major Cytogenetic Response After 6 and 12 Months of Treatment.
timeFrame: 6 and 12 months after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Brian J. Druker, MD
role: STUDY_CHAIR
References: