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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Complete Cytogenetic Response at 6 and 12 Months (Phase II)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •18 and over
- •Performance status:
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •See Disease Characteristics
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •AST or ALT no greater than 2 times ULN
- •Creatinine no greater than 1.5 times ULN
- •Cardiovascular:
- •No New York Heart Association class III or IV heart disease
- •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
- 另有 4 项未显示
排除标准
- 未提供
结局指标
主要结局
Complete Cytogenetic Response at 6 and 12 Months (Phase II)
时间窗: At 6 and 12 months during 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%).
Minor Cytogenetic Response at 6 and 12 Months (Phase II)
时间窗: At 6 and 12 months during phase II
Complete Hematologic Response at 6 and 12 Months (Phase II)
时间窗: At 6 and 12 months during phase II
Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)
时间窗: 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)
时间窗: 12 Months
1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death
Major Cytogenetic Response After 6 and 12 Months of Treatment.
时间窗: 6 and 12 months after 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.
次要结局
未报告次要终点