A Phase II Study of CCI-779 in B-cell Lymphoma and CLL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 13
- 主要终点
- Objective Overall Response Rate
研究概览
简要总结
Drugs used in chemotherapy, such as CCI-779, work in different ways to stop cancer cells from dividing so they stop growing or die. This phase II trial is studying how well CCI-779 works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
详细描述
PRIMARY OBJECTIVES:
I. Determine the complete and partial response rate in patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with CCI-779.
II. Determine the toxicity and safety of this drug in these patients. III. Correlate the degree of activation of P13/AKT/mTOR pathway and levels of CDK inhibitors with response in patients treated with this drug.
IV. Correlate CCI-779 induced inactivation of mTOR with response in these patients.
OUTLINE: Patients are stratified according to disease (aggressive lymphoma [group A] vs follicular lymphoma [group B] vs small lymphocytic lymphoma or chronic lymphocytic leukemia [group C]).
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 B-cell non-Hodgkin's lymphoma, including the following subtypes:
- •Aggressive B-cell lymphoma (Group A)
- •Diffuse large B-cell lymphoma
- •Transformed lymphoma
- •Follicular lymphoma (Group B)
- •Small lymphocytic lymphoma
- •Chronic lymphocytic leukemia (CLL) (Group C)
- •Other B-cell small lymphocytic disorders
- •No mantle cell lymphoma
- •No potentially curative treatment options because of lack of response, relapse, or ineligibility
- •Relapsed or refractory disease
- •Patients with refractory disease (i.e., less than a partial response to the last treatment) must have received no more than 3 prior regimens (group A)
- •Patients with sensitive disease (i.e., at least a partial response to the last treatment) must have received no more than 4 prior regimens (group A)
- •Patients who have failed prior autologous transplantation are eligible (group A)
- •No more than 5 prior regimens (groups B and C)
- •The salvage regimen, conditioning regimen, and any maintenance therapy are considered 1 regimen
- •Prior rituximab or alemtuzumab is not considered prior therapy
- •No limitation to the amount of prior radiotherapy
- •No CNS involvement
- •Performance status: ECOG 0-2 OR Karnofsky 60-100%
- •Life expectancy more than 3 months
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No prior allergic reactions attributed to compounds of similar chemical or biological composition to CCI-779
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Completed therapy and considered < 30% risk of relapse
- •No other concurrent uncontrolled illness
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No concurrent prophylactic hematopoietic colony-stimulating factors
- •No concurrent pegfilgrastim
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •More than 4 weeks since prior radiotherapy and recovered
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum (St. John's wort)
- •No other concurrent known inducers of CYP3A4
- •No other concurrent investigational agents
- •No other concurrent anticancer therapy
- •Measurable disease*
- •At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan [Note: *Only bone marrow or peripheral blood involvement required for CLL and Waldenstrom's macroglobulinemia ]
- •Absolute neutrophil count >= 1,000/mm3
- •Bilirubin =< 1.5 times upper limit of normal (ULN)
- •AST and ALT =< 2.5 times ULN
- •Creatinine =< 1.5 times ULN
- •Fasting cholesterol =< 350 mg/dL
- •Fasting triglycerides =< 400 mg/dL
- •Platelet count >= 50, 000/mm3 (> 20,000/mm3 for patients with thrombocytopenia due to bone marrow involvement)
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks.
干预措施: temsirolimus (Drug)
结局指标
主要结局
Objective Overall Response Rate
时间窗: Up to 6 years
The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10655437#) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires \>=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR.
Duration of Response
时间窗: Up to 6 years
Duration of response was the time from date of response to date of progression and evaluated among participants with response. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy.
Overall Survival
时间窗: Up to 6 years
The overall survival was evaluated using the Kaplan-Meier estimator.
次要结局
未报告次要终点