Phase I/II Study of Lenalidomide (Revlimid), Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R2CHOP) Chemoimmunotherapy in Patients With Newly Diagnosed Diffuse Large Cell and Follicular Grade IIIA/B B Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 138
- 试验地点
- 3
- 主要终点
- Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)
研究概览
简要总结
RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large cell or follicular B-cell lymphoma.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of lenalidomide when given in combination with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with newly diagnosed stage II-IV diffuse large cell or grade 3 follicular B-cell lymphoma. (Phase I)
- To assess the efficacy of this regimen, in terms of event-free survival and response rate, in these patients. (Phase II)
- To assess the safety of this regimen in these patients. (Phase II)
Secondary
- To assess the host immune function at baseline and after treatment and correlate these parameters with tumor response and event-free survival.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed diffuse large cell or grade 3A/B follicular lymphoma
- •Newly diagnosed disease
- •Stage II, III, or IV disease
- •Measurable disease, defined as ≥ 1 lesion ≥ 1.5 cm in one diameter, as detected by CT scan or PET-CT scan (PET/CT fusion)
- •CD20-positive disease
- •No post-transplant lymphoproliferative disorder (PTLD)
- •No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •ANC ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal
- •Alkaline phosphatase ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma)
- •AST ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma)
- •Creatinine ≤ 2 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile female patients must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 28 days after completion of study therapy
- •Fertile male patients must use effective contraception during and for ≥ 28 days after completion of study therapy, even if they have had a successful vasectomy
- •No blood, sperm, or semen donation during and for ≥ 28 days after completion of study therapy
- •Willing to return to enrolling institution for follow-up
- •Willing to provide blood samples for translational research purposes
- •No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would preclude study entry or significantly interfere with the proper assessment of safety and toxicity of the prescribed study regimen
- •No known HIV positivity
- •Not immunocompromised
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness/social situation that would preclude compliance with study requirements
- •No other active malignancy, except localized nonmelanotic skin cancer or any cancer that, in the judgment of the investigator, has been treated with curative intent and will not interfere with the study treatment plan and response assessment
- •No myocardial infarction within the past 6 months
- •No congestive heart failure requiring ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Ejection fraction ≥ 45% by MUGA or ECHO
- •No history of life threatening or recurrent thrombosis/embolism (unless on anticoagulation therapy during study treatment)
- •PRIOR CONCURRENT THERAPY:
- •No prior radiotherapy to ≥ 25% of the bone marrow
- •No concurrent erythroid-stimulating agents (e.g., Procrit, Aranesp)
- •No other concurrent treatment for lymphoma
- •No concurrent radiotherapy, chemotherapy, or immunotherapy for another active malignancy
- •Able to receive concurrent prophylactic anticoagulation therapy (e.g., low-dose aspirin [81 mg] daily or an alternative prophylaxis [e.g., warfarin or low molecular weight heparin])
排除标准
- 未提供
结局指标
主要结局
Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)
时间窗: 5 years
Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)
时间窗: 1 year
Other Phase II Cohorts were not evaluable for event-free survival analysis.
Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite)
时间窗: 2 years
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Other Phase II Cohorts were not evaluable for progression-free survival analysis.
次要结局
- Correlation of Immune Function With Clinical Outcomes(5 years)
- Event-free Survival(5 years)
- Overall Survival(5 years)
- Progression-free Survival(5 years)
- Duration of Response(5 years)
- Immune Function Before and After Treatment as Assessed by T-, B-, and NK-cell Quantification(5 years)
- Overall Response Rate(When all patients either have a CR or have completed observation.)
- Overall Complete Response Rate(When all patients either have a CR or have completed observation.)