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)
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
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 indefinitely to
check on your health and for information about any other cancer treatments you may have
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose
Toxicity assessments at 4 Weeks for Cycle 1, 28 days for subsequent cycles
Michael Wang, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
|UT MD Anderson Cancer Center||Houston, Texas 77030|