A Phase I Study of PS-341 (Velcade, Bortezomib) in Combination With 17-allylamino-17-demethoxygeldanamycin (17-AAG) in Patients With Relapsed or Refractory Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of bortezomib) in combination with 17-AAG)
研究概览
简要总结
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin and bortezomib in treating patients with relapsed or refractory hematologic cancer. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of PS-341 (Velcade, Bortezomib) in combination with 17-allyamino-17-demethoxygeldanamycin (17-AAG) in patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).
II. To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL).
III. To define the specific toxicities and the dose limiting toxicity (DLT) of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:
- •Acute myeloid leukemia or acute lymphoblastic leukemia
- •Not a candidate for potentially curative therapy
- •WBC ≤ 10,000/mm^3 OR WBC ≤ 40,000/mm^3 that is stable for 5 days (hydroxyurea allowed)
- •No acute promyelocytic leukemia
- •Non-Hodgkin's lymphoma (NHL), including 1 of the following subtypes:
- •Small lymphocytic lymphoma
- •Marginal zone lymphoma
- •Lymphoplasmacytic lymphoma
- •Follicular lymphoma
- •Mantle cell lymphoma
- •Diffuse large B-cell lymphoma
- •Anaplastic large cell lymphoma
- •Peripheral T-cell lymphoma
- •Extranodal NK/T cell lymphoma (nasal and nasal type)
- •Enteropathy-type T-cell lymphoma
- •Hepatosplenic T-cell lymphoma
- •Angioimmunoblastic T-cell lymphoma
- •Subcutaneous panniculitis-like T-cell lymphoma
- •Chronic lymphocytic leukemia (CLL)
- •Patients with NHL or CLL must meet the following criteria:
- •Ineligible for, or refused potentially curative stem cell transplantation
- •Transformed lymphoma/Richter's transformation, defined as the transformation of low-grade lymphoma, including follicular lymphoma, CLL, or small lymphocytic lymphoma to high-grade lymphoma (i.e., diffuse large cell lymphoma) allowed at time of transformation
- •Evidence of ≥ 50% bone marrow involvement at the time of enrollment OR tumor tissue accessible for biopsy (for patients enrolled after the maximum tolerated dose [MTD] is determined)
- •Absolute neutrophil count ≥ 1,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Relapsed or refractory disease
- •Willing to undergo serial bone marrow biopsy (for patients enrolled after the MTD is determined)
- •No untreated or active CNS leukemia or lymphoma
- •Performance status - ECOG 0-2
- •At least 12 weeks
- •Bilirubin ≤ 1.5 mg/dL
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Creatinine ≤ 2.0 mg/dL
- •No uncontrolled cardiac disease
- •No New York Heart Association class III-IV symptomatic congestive heart failure
- •No unstable angina pectoris
- •No serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation > 3 beats in a row) within the past 6 months
- •No other uncontrolled cardiac arrhythmia or requiring antiarrhythmic drugs
- •No myocardial infarction within the past year
- •No active ischemic heart disease within the past year
- •No congenital long QT syndrome
- •No left bundle branch block
- •QTc ≥ 450 msec (for men) or 470 (for women) on ECG/EKG
- •No history of LVEF < 50% by MUGA or echocardiogram
- •Resting ejection fraction ≥ 50% by MUGA or echocardiogram
- •No prior history of cardiac toxicity after receiving anthracycline therapy (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, or mitoxantrone hydrochloride)
- •No uncontrolled pulmonary disease
- •No symptomatic pulmonary disease requiring oxygen or medications
- •DLCO (i.e., oxygen diffusion capacity) ≥ 80% on pulmonary function testing
- 另有 28 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (17-AAG and bortezomib)
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.
干预措施: tanespimycin (Drug)
Treatment (17-AAG and bortezomib)
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-6 hours on days 1, 4, 8, and 11 and bortezomib IV over 3-5 seconds on days 4, 8, and 11 of course 1 and on days 1, 4, 8, and 11 of all subsequent courses.
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit. Patients achieving objective response may discontinue therapy to undergo stem cell transplantation.
干预措施: bortezomib (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of bortezomib) in combination with 17-AAG)
时间窗: Day 21
Defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
次要结局
未报告次要终点