Lenalidomide and Rituximab Treatment of Relapsed Mantle Cell Lymphoma and Diffuse Large B-Cell Non-Hodgkin's Lymphoma, Transformed Large Cell Lymphoma, and/or Grade 3 Follicular Lymphoma (Follicular Cleaved Large Cell Lymphoma or Follicular Non-Cleaved Large Cell Lymphoma (RV-LYM-PI-0056)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the drug lenalidomide (Revlimid, lenalidomide) that can be given with Rituxan® (rituximab) in the treatment of relapsed mantle cell lymphoma. The safety and effectiveness of this combination treatment will also be studied in both mantle cell lymphoma and diffuse large B-cell non-Hodgkin's lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma).
详细描述
Rituximab is a type of drug known as a monoclonal antibody. It is designed to act against the cluster of differentiation antigen 20 (CD20) antigen that is found on the surface of both normal B lymphocytes or on the malignant lymphoma cells. When rituximab attacks the CD20 antigen, it can kill the lymphoma cells. lenalidomide is known as an immunomodulatory drug. It is thought to work by helping the immune system fight disease.
If you are found to be eligible, you will receive lenalidomide plus rituximab. This study will be done in 2 phases. In the Phase I portion of this study, 6 dose levels of lenalidomide will be studied. The same level of rituximab will be given to all participants. Between 3-6 participants will be treated at each dose level. Those enrolled first on this study will receive the lowest dose of lenalidomide plus rituximab. After treatment, each dose level of lenalidomide will be evaluated to check for any intolerable side effects. The dose of lenalidomide that you will receive will depend on the time that you enter this study and the side effects of those participants that entered the study before you. Once a dose has been assigned to you, it will not increase, but it could decrease or remain the same for a while if you have intolerable side effects. Once the highest tolerable dose of lenalidomide has been found, additional participants will receive that dose during the Phase II portion of this study.
You should swallow lenalidomide capsules whole by mouth every day at the same time, with a glass of water on either a full or an empty stomach. Do not break, chew or open the capsules. This will continue for 21 days, followed by a 7-day rest period. Each 28-day period is called a cycle of therapy.
If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).
During Cycle 1 only, you will also take rituximab by vein once a week for 4 weeks (total of 4 doses). The first rituximab infusion (by vein) usually takes 6 to 8 hours. Later infusions are generally shorter, taking about 4 hours to complete. For participants who have a large mass or who have lymphoma cells in their blood, the rituximab dose may be split into a 2-day infusion. Vital signs (temperature, blood pressure, respiration, and heart rate) will be monitored just before, during, and after the infusions. There will be an observation period of about 1 hour after the end of each rituximab infusion, after which you will be allowed to go home.
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
- •Phase I and Phase II: Confirmed diagnosis of mantle cell lymphoma with CD20 positivity in tissue biopsy. Patients must have previously treated relapsed and/or refractory MCL. Or for Phase II: Confirmed diagnosis of previously treated relapsed and/or refractory diffuse large B-cell lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma).
- •Understand and voluntarily sign an Institutional Review Board (IRB) approved informed consent form.
- •Age equal to or greater than 18 years at the time of signing the informed consent.
- •Patients must have bi-dimensional measurable disease (bone marrow only involvement is acceptable).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
- •Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl; platelet count >75,000/mm^3 and absolute neutrophil count (ANC) > 1,000/mm^
- •AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present.
- •Disease free of prior malignancies of equal to or greater than 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years.
- •Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test 10-14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide.
- •Continuation from # 8 : (HIGHLY EFFECTIVE METHODS - Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation, partner's vasectomy. ADDITIONAL EFFECTIVE METHOD-latex condom, diaphragm, cervical cap) while on study drug.
- •WCBP must agree to have pregnancy tests every week for the first 4 weeks of treatment, then every 4 weeks if her menstrual cycles are regular or every 2 weeks if her cycles are irregular, while on study drug, and 4 weeks after the last dose of study drug. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
- •Patients may have 1 to 4 lines of prior therapy for MCL (projected median 2 prior lines of therapy). Patient may or may not have received an anthracycline-based chemotherapy regimen.
- •Patients must be willing to receive transfusions of blood products.
- •Past stem cell (autologous or allogenic) transplantation is acceptable.
- •Patients may have prior therapy with rituximab.
排除标准
- •Any serious medical condition including but not limited to, uncontrolled hypertension, diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active infection, active hemorrhage, laboratory abnormality, or psychiatric illness that places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. Patients with history of cardiac arrythmias should have cardiac evaluation and clearance.
- •Pregnant or lactating females.
- •Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment.
- •Known hypersensitivity to thalidomide or rituximab; including the development of erythema nodosum if characterized by a desquamating rash while taking thalidomide.
- •Prior use of lenalidomide.
- •Known HIV infection. Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; not including patients with positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation.
- •All patients with history of central nervous system lymphoma.
- •Patients with peripheral blood involvement with white blood cell count (WBC) > 20,000 are EXCLUDED for the Phase I component of the study.
- •Patients with >/= Grade 3 neuropathy.
- •Patients with active pulmonary embolism or deep vein thrombosis (30 days within diagnosis).
- •Patients with severe bradycardia (heart rate <40 bpm, hypotension, light-headedness, syncope).
研究组 & 干预措施
Lenalidomide + Rituximab
Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
干预措施: Rituximab (Drug)
Lenalidomide + Rituximab
Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab
时间窗: 28 days of cycle 1
MTD is defined as the highest dose level in which 1 or fewer participants experienced a dose limiting toxicity (DLT) in 6 participants treated. DLT is any grade III or IV toxicity during the first 28 days (first cycle) of therapy.
次要结局
- Response of Participants Treated at Lenalidomide 20 mg(56 days, assessed after 2 cycles)
- Objective Response Rate of Participants Treated With Lenalidomide 20 mg: Overall Response as % of Participants With Complete or Partial Response(56 days)