Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 11
- 主要终点
- Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only
研究概览
简要总结
This phase I/II trial studies the side effects and the best dose of lenalidomide when given together with temsirolimus and to see how well it works in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of improvement or is not responding to treatment. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of Hodgkin lymphoma or non-Hodgkin lymphoma by blocking blood flow to the cancer. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety, toxicity, and maximum tolerated dose of lenalidomide when combined with temsirolimus in patients with relapsed lymphomas. (Phase I) II. To determine complete and overall response rate of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: follicular lymphoma, diffuse large B-cell lymphoma, and lymphoma not otherwise specified (NOS) (including Hodgkin lymphoma, T-cell non-Hodgkin lymphoma [T-NHL], lymphoplasmacytic lymphoma, and mantle cell lymphoma). (Phase II) III. To determine duration of response, progression-free survival, and overall survival of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: diffuse large B-cell lymphoma, follicular lymphoma, and lymphoma NOS (including Hodgkin lymphoma, T-NHL, lymphoplasmacytic lymphoma, mantle cell lymphoma). (Phase II)
SECONDARY OBJECTIVES:
I. To determine mammalian target of rapamycin (mTOR) pathway activation in pre-treatment tumor tissue.
II. To determine angiogenic and microenvironmental status of pre-treatment tissue and peripheral blood samples, and to evaluate changes following treatment with temsirolimus and lenalidomide.
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
- •Histology: bone marrow biopsies (with the exception of lymphoplasmacytic lymphoma) as the sole means of diagnosis are not acceptable; fine needle aspirates are not acceptable
- •Phase I: previously treated, histologically confirmed Hodgkin and non-Hodgkin lymphomas; the only exception to a requirement for a lymph node biopsy is lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein
- •Phase II: previously treated, histologically confirmed mature non-Hodgkin lymphoma (NHL) stratified by histology:
- •Group A: diffuse large B-cell lymphoma (NOTE: all patients with DLBCL must have germinal center vs. non-germinal center phenotype established via immunohistochemistry)
- •Group B: follicular lymphoma
- •Group C: lymphoma NOS (including Hodgkin lymphoma, T-NHL, marginal zone lymphoma, lymphoplasmacytic
- •No limit to number of prior therapies; prior autologous transplantation is allowed
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Absolute neutrophil count (ANC) >= 1,000/uL
- •Platelet count >= 75,000/uL
- •Total bilirubin =< 1.5 times upper limit of normal (ULN) (unless due to Gilbert's)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
- •Creatinine clearance >= 60 mL/min as determined by calculated Cockcroft-Gault equation
- •Fasting serum cholesterol =< 350 mg/dL
- •Fasting serum triglycerides =< 2.5 times ULN
- •All patients are required to have measurable disease; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:
- •Bone lesions (lesions if present should be noted)
- •Pleural/pericardial effusion
- •Lymphangitis cutis/pulmonis
- •Bone marrow (involvement by lymphoma should be noted)
- •For Waldenstrom's macroglobulinemia, measurable disease is defined as at least one lesion with a single diameter of greater than 2 cm by computed tomography or bone marrow involvement with greater than 10% malignant cells and quantitative monoclonal protein (immunoglobulin M [IgM], IgG, IgA) greater than 1,000 mg/dL
- •Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- •Ability to understand and the willingness to sign a written informed consent document
- •Patients who are human immunodeficiency virus (HIV) positive are allowed to participate BUT must meet the following criteria:
- •No acquired immune deficiency syndrome (AIDS)-defining illness, AND
- •Cluster of differentiation (CD) 4 count >= 400 cells/mm^3, AND
- •No anti-retroviral therapy (including high-active antiretroviral therapy [HAART]) within 7 days of starting protocol therapy, AND
- •Patient may not take concurrent anti-retroviral therapy (including HAART) while on protocol
- •NOTE: it is not generally recommended to suspend anti-retroviral therapy (including HAART); the medical team enrolling a patient who suspends anti-retroviral therapy for the purpose of study participation must have a documented note reviewing the potential risks/benefits with the patient in the medical chart
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients who are receiving any other investigational agents
- •Patients with known brain metastases should be excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or lenalidomide used in study
- •Patients requiring active anti-retroviral therapy for HIV are excluded
- •No "currently active" second malignancy, other than non-melanoma skin cancers; patients are not considered to have a "currently active" second malignancy if they have completed anti-cancer therapy and are considered by their physicians to be at less than 30% risk of relapse
- •No history (within 3 months of study entry) of deep venous thrombosis/pulmonary embolism (DVT/PE); patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but should receive prophylactic aspirin or low molecular weight heparin
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients with relapsed/refractory DLBCL or HL who are eligible and willing to undergo potentially curative stem cell transplant
- •Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are excluded
- •No corticosteroids within 14 days prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 10 mg/day prednisone or equivalent; any patient on steroid therapy must receive thromboembolic prophylaxis
研究组 & 干预措施
Treatment (lenalidomide, temsirolimus)
Patients receive lenalidomide PO on days 1-21 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (lenalidomide, temsirolimus)
Patients receive lenalidomide PO on days 1-21 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.
干预措施: Lenalidomide (Drug)
Treatment (lenalidomide, temsirolimus)
Patients receive lenalidomide PO on days 1-21 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.
干预措施: Temsirolimus (Drug)
结局指标
主要结局
Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only
时间窗: 28 days
Incidence of dose-limiting toxicity (DLT) defined as any grade 3 or 4 adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Complete Response (Phase II)
时间窗: Up to 1 year
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions;
Overall Response Rate (Phase II)
时间窗: Up to 1 year
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
- Progression-free Survival (PFS) (Phase II)(Time from study entry until disease progression or death from any cause, assessed up to 5 years)
- Overall Survival (OS) (Phase II)(Time from study entry until death from any cause, assessed up to 6 years)