Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma
|ClinicalTrials.gov Identifier: NCT00294632|
Recruitment Status : Completed
First Posted : February 22, 2006
Last Update Posted : February 4, 2016
|First Submitted Date ICMJE||February 20, 2006|
|First Posted Date ICMJE||February 22, 2006|
|Last Update Posted Date||February 4, 2016|
|Study Start Date ICMJE||February 2006|
|Actual Primary Completion Date||February 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Maximum Tolerated Dose (MTD) of Lenalidomide in Combination with Rituximab i [ Time Frame: 28 days ]
MTD is defined as the highest dose level in which 1 or fewer pts experienced a dose limiting toxicity (DLT) in 6 pts treated. DLT is any grade III or IV toxicity during the first 28 days (first cycle) of therapy.
|Original Primary Outcome Measures ICMJE
||To evaluate the safety of CC-5013 in combination with rituximab in patients with relapsed/refractory mantle cell lymphoma (MCL).|
|Change History||Complete list of historical versions of study NCT00294632 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Objective Response Rate [ Time Frame: 56 days ]
Objective response rate defined as complete or partial response after 2 cycles of therapy maintained for one month. Objective response monitored using Simon's optimal 2-stage design.
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma|
|Official Title ICMJE||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)|
|Brief Summary||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).|
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.
You will be given a diary to record when you take all of the study medications and any problems or illnesses you experience. You should also write down in the diary any other medications you take while you are on this study.
After you begin your treatment on the study drug, you will have check-up visits weekly for the first cycle, every 2 weeks for Cycles 2 and 3 of therapy, and then once a month for the rest of the study. If your doctor feels it is necessary, the check-up visits may take place more often. At the end of each 28-day treatment cycle, you will have a visit with the study doctor to see if it is safe for you to continue on this study and make sure the cancer has not gotten worse. If at the end of the each cycle, your doctor believes that you are eligible to continue (based on the degree and type of side effects you are having and the response of the cancer to the study drug), you will receive enough study drug for another 28-day treatment cycle.
At these visits you will have a complete physical exam, including measurement of vital signs. You will be asked questions about how you have felt since your last visit. All medications you have taken since your last visit will be reviewed by the study doctor. You should bring the empty pill packages and any unused medication along with the diary you were given earlier to each visit. You will have a blood sample collected (around 8 tablespoons) for routine blood tests to check on the status of the disease.
If you are eligible to continue on this study, a new 28-day supply of lenalidomide capsules will be given to you at this visit. Other tests may be done at these visits to check on the status of the disease. You may have a sample of bone marrow collected and/or have either x-rays or CT scans, positron emission tomography (PET) scan (if needed), and gastrointestinal endoscopy (for patients with known or suspected site of disease) to evaluate your response to therapy. These tests may not be done at every check-up visit. They will be done when your doctor feels they are necessary. You may have unscheduled visits at any time during this study if your doctor feels it is necessary for your care.
You may continue to receive treatment as long as the cancer does not get worse and you do not experience any intolerable side effects. If, at any time during treatment, the disease gets worse or you experience any intolerable side effects, you will be taken off this study, and your doctor will discuss other treatment options with you. The number of weeks you are on the study drug depends on how well you are tolerating the study drug and how well the lymphoma responds to the study drugs.
After your participation in this study ends, and if you have completed cycle 1 or more, you will have an end-of-study visit. At this visit you will have a complete physical exam, including measurement of vital signs and weight. You will have an ECG and you will be asked questions about how you have felt since your last visit. All medications you have taken since your last visit will be reviewed by the study doctor. You will have a blood sample collected (around 3 tablespoons) for routine blood tests to check on the status of the disease. You will have bone marrow collected for tests and have either x-rays or CT scans of your body to check on the status of the disease. You should return all empty drug packaging as well as any unused lenalidomide capsules at this visit.
If you completed at least 12 and no more than 24 cycles of treatment with lenalidomide, you will have follow-up visits every 3 months. If you complete 24 or more cycles of treatment with lenalidomide, you will have follow-up visits every 6 months. This will continue until the disease gets worse. At each visit, blood (about 1 teaspoon) will be drawn to test your thyroid function. The status of your disease will be evaluated and you may have a bone marrow biopsy and aspirate. You will have a chest x-ray and CT scans of the chest, abdomen, and pelvis. If needed, you will also have a CT scan of the neck. If needed, you will have a colonoscopy or endoscopy. You may also have a bone marrow biopsy and aspirate performed.
After the end-of-study visit, you will be contacted by phone every 6 months until March 15, 2015, to check on your health and for information about any other cancer treatments you may have received.
This is an investigational study. Lenalidomide is FDA approved and commercially available. Lenalidomide is approved for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes associated with the chromosome 5 abnormality with or without other chromosome abnormalities. Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy. Its use in this study, for relapsed mantle cell lymphoma or large B-cell Non-Hodgkin's lymphoma, is investigational. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental.
Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphomas.
Up to 71 participants with mantle cell lymphoma and 41 participants with 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) will take part in this study. All will be enrolled at MD Anderson.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: Lenalidomide + Rituximab
Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
|Publications *||Wang M, Fayad L, Wagner-Bartak N, Zhang L, Hagemeister F, Neelapu SS, Samaniego F, McLaughlin P, Fanale M, Younes A, Cabanillas F, Fowler N, Newberry KJ, Sun L, Young KH, Champlin R, Kwak L, Feng L, Badillo M, Bejarano M, Hartig K, Chen W, Chen Y, Byrne C, Bell N, Zeldis J, Romaguera J. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol. 2012 Jul;13(7):716-23. doi: 10.1016/S1470-2045(12)70200-0. Epub 2012 Jun 6.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date||February 2016|
|Actual Primary Completion Date||February 2016 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00294632|
|Other Study ID Numbers ICMJE||2005-0461
NCI-2012-01356 ( Registry Identifier: NCI CTRP )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|Collaborators ICMJE||Celgene Corporation|
|PRS Account||M.D. Anderson Cancer Center|
|Verification Date||February 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP