Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma
1. To evaluate the safety of lenalidomide in combination with rituximab in patients with relapsed/refractory mantle cell lymphoma (MCL) 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).
2. To evaluate the response rate of lenalidomide in combination with rituximab in patients with relapsed or refractory 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).
3. To evaluate the survival of mantle cell lymphoma patients treated with lenalidomide and rituximab 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 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, 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.
After the end-of-study visit, you will be contacted by phone every 6 months indefinitely 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 M. D. Anderson.
Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00294632
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.
Precursor T-cell Lymphoblastic Leukemia-lymphoma
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Two or more distinct types of malignant lymphoid tumors occurring within a single organ or tissue at the same time. It may contain different types of non-Hodgkin lymphoma cells or both Hodgkin and non-Hodgkin lymphoma cells.
Lymphoma, Large-cell, Anaplastic
A systemic, large-cell, non-Hodgkin, malignant lymphoma characterized by cells with pleomorphic appearance and expressing the CD30 ANTIGEN. These so-called "hallmark" cells have lobulated and indented nuclei. This lymphoma is often mistaken for metastatic carcinoma and MALIGNANT HISTIOCYTOSIS.
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