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
18 Years
N/A
Both
Leukemia
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete Cytogenetic Response at 6 and 12 Months (Phase II)
Outcome Description:
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%).
Outcome Time Frame:
At 6 and 12 months during phase II
Safety Issue:
No
Principal Investigator
Brian J. Druker, MD
Investigator Role:
Study Chair
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000068443
NCT ID:
NCT00015847
Start Date:
April 2001
Completion Date:
May 2011
Related Keywords:
- Leukemia
- relapsing chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- Philadelphia chromosome positive chronic myelogenous leukemia
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
| OHSU Knight Cancer Institute | Portland, Oregon 97239 |
