Study Drug Administration:
Each cycle is 28 days.
If participant is found to be eligible to take part in this study, participant will take 4
ibrutinib capsules with 1 cup (about 8 ounces) of water each day. Participant should take
ibrutinib in the morning and at the same time as participant takes lenalidomide (described
below). Do not open the capsules or dissolve them.
If participant misses a dose, participant can take it up to 6 hours after the time
participant would have taken it. If it is later than 6 hours, participant should skip the
dose and start taking the capsules at the same time as usual the next day. Participant will
need to fill out diary cards with information about when participant takes ibrutinib.
Participant should bring the diary cards with participant to appointments. Participant will
receive a 30 day supply of the ibrutinib capsules on Day 1 of Cycles 1-11. After that,
starting on Cycle 12 and then every other cycle after that (Cycles 14, 16, and so on),
participant will receive a 60-day supply of the drug every other cycle.
Participant will take lenalidomide by mouth on Days 1-21 of each cycle. Participant should
take lenalidomide at the same time each day. Participant should take it with a glass of water
on either a full or an empty stomach. Participant should not break, chew, or open the
If participant misses a dose of lenalidomide, participant should take it as soon as
participant remembers on the same day. If participant misses taking participant's dose for
the entire day, participant should take participant's regular dose the next scheduled day.
Participant should not take double participant's regular dose to make up for a missed dose.
If participant takes more than the prescribed dose of lenalidomide, participant should seek
emergency medical care if needed and contact study staff right away.
Participant will also be given standard drugs to help decrease the risk of side effects.
Participant may ask the study staff for information about how the drugs are given and their
Participant will receive rituximab by vein on Days 1, 8, 15, and 22 of Cycles 1 and 2. After
that, participant will receive rituximab by vein on Day 1 of Cycles 3-8 and then every other
cycle after that (Cycles 10, 12, 14, and so on). The first dose should take about 6-8 hours.
After that, each dose should take about 4 hours.
If the doctor thinks it is in participant's best interest, participant may receive rituximab
for a period of over 2 days. Participant's doctor will tell if participant will receive the
dose over 2 days.
Length of Study:
Participant may continue taking ibrutinib for as long as the doctor thinks it is in
participant's best interest. Participant may continue taking lenalidomide for up to 1 year.
Participant may continue taking rituximab for up to 2 years. Participant will no longer be
able to take the drug if the disease gets worse, if intolerable side effects occur, or if
participant is unable to follow study directions.
Participation will be over after follow-up.
On Day 1 of Cycle 1:
- Blood (about 2 tablespoons) will be drawn to check the status of the disease and for
biomarker testing, which may include genetic biomarkers. Biomarkers are found in the
blood and may be related to participant's reaction to the study drug.
- Blood (about 2 tablespoons) will be drawn to check participant's immune system.
- Blood (about 2 tablespoons) will be drawn for tumor lysis syndrome monitoring if needed.
On Day 1 of Cycles 1-12 and then every other cycle after that (Cycles 14, 16, 18, and so on):
- Participant will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
On Days 8, 15, and 22 of Cycle 1, blood (about 3 tablespoons) will be drawn for routine tests
and tumor lysis syndrome monitoring if needed.
On Day 1 of Cycles 2, 4, 6, 8, then every 4 cycles after that (Cycles 12, 16, 20, and so on),
participant will have a CT scan to check the status of the disease. If the doctor thinks it
is in participant's best interest, participant may have these scans less often.
One (1) time between Cycles 2-10, when the study doctor thinks it is needed or if the disease
gets worse, blood (about 4 tablespoons) will be drawn for biomarker testing and to check
participant's immune system.
Every 14 days, if the doctor thinks it is needed and if participant is able to become
pregnant, blood (about 1½ tablespoons) or urine will be collected for a pregnancy test.
At any time during the study, if the study doctor thinks it is needed:
- Participant may have a bone marrow biopsy and/or aspiration.
- Participant may have a gastrointestinal endoscopy.
- Participant may have a PET/CT scan
- If participant can become pregnant, blood (about 1½ tablespoons) or urine may be
collected for a pregnancy test.
Within 30 days after participant's last dose of study drugs:
- Participant will have a physical exam.
- Participant will have an EKG.
- Blood (about 5-7 tablespoons) will be drawn for routine tests, for biomarker testing,
for immune system testing, and to check the status of the disease.
- Participant will have an x-ray.
- If the doctor thinks it is needed, participant will have a CT scan and/or a PET/CT scan
to check the status of the disease.
- If the doctor thinks it is needed, participant will have a gastrointestinal endoscopy to
check the status of the disease.
- If the doctor thinks it is needed, participant will have a bone marrow biopsy and/or
aspirate to check the status of the disease.
- If participant can become pregnant, blood (about 1½ tablespoons) or urine will be
collected for a pregnancy test.
Long Term Follow-Up:
After participant's end-of-treatment visit, a member of the study staff will contact
participant by phone every 3 months for 1 year and then every 6 months after that to see how
participant is doing. These calls will take about 2-3 minutes.
This is an investigational study. Ibrutinib is FDA approved and commercially available for
the treatment of MCL. Rituximab is FDA approved for the treatment of non-Hodgkin's lymphoma
and certain types of leukemia. Lenalidomide is FDA approved for the treatment of
The use of these drugs in combination is investigational. The study doctor can explain how
the study drugs are designed to work.
Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.
1. Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.
2. Ki-67 >/= 50%.
3. Patients must have never received any prior systemic therapy for their disease.
4. Sign (or their legally-acceptable representatives must sign) an informed consent
document indicating that they understand the purpose of and procedures required for
the study and are willing to participate in the study.
5. Age > 65 years at the time of signing the informed consent.
6. Patients should in general have bi-dimensional measurable disease using the Cheson
criteria (Measureable disease by computed tomography (CT) scan defined as at least 1
lesion that measures =/>1.5 cm in single dimension) (bone marrow or gastrointestinal
(GI) only involvement is acceptable).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
8. Absolute neutrophil count (ANC) >/= 1000/mm^3 without transfusion support
9. Platelet count > 100,000/mm^3. Patients who have bone marrow infiltration by MCL are
eligible if their platelet level is >/= 50,000 /mm^3 independent of platelet
10. aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) </= 3 x upper limit
11. Serum bilirubin <1.5 mg/dl unless bilirubin rise is due to Gilbert's syndrome or of
12. Creatinine (Cr) Clearance >/= 25 mL/min (per Cockcroft-Gault Equation ),
13. Disease free of prior malignancies of equal to or greater than 6 months 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.
14. Patients must be willing to receive transfusions of blood products.
15. Willing and able to participate in all study related procedures and therapy including
swallowing capsules without difficulty.
16. Men must agree 1) to use a latex condom during sexual contact with a FCBP even if they
have had a vasectomy from the time of signing the informed consent form through 90
days after the last dose of lenalidomide and ibrutinib;2) to not donate sperm during
and after the study. Females of childbearing potential (FCBP)* must have a negative
serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14
days prior to and again within 24 hours of starting lenalidomide and must either
commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
methods of birth control, one highly effective method (11.8) and one additional
effective method AT THE SAME TIME, at least 28 days before she starts taking
lenalidomide through 90 days and ibrutinib through 30 days after the last dose of
study drug. FCBP must also agree to ongoing pregnancy testing.
17. All patients must be registered in and must comply with all requirements of the
Revlimid Rems™ program.
1. Any serious medical condition that, in the investigator opinion, places the patient at
unacceptable risk and/or would prevent the subject from signing the informed consent
form. Examples include but are not limited to, uncontrolled hypertension, uncontrolled
diabetes mellitus, active/symptomatic coronary artery disease, active infection
requiring treatment with intravenous (IV) antibiotics, antiviral or antifungal agents,
active hemorrhage, or psychiatric illness in the investigator's opinion places the
patient at unacceptable risk and would prevent the subject from signing the informed
2. Pregnant or breastfeeding females.
3. Known human immunodeficiency virus (HIV) infection. Patients with active hepatitis B
infection (not including patients with prior hepatitis B vaccination; or positive
serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there
is no active disease. These patients should be optimized by GI consultation for
Hepatitis B and Infectious Disease consult for Hepatitis C.
4. The patient has a prior or concurrent malignancy that in the opinion of the
investigator, presents a greater risk to the patient's health and survival, than of
the MCL, within the subsequent 6 months at the time of consent.
5. History of stroke or intracranial hemorrhage within 6 months prior to signing the
6. Patients at high-risk for thromboembolic disease, such as those with prior heterotopic
ossification (h/o) deep venous thrombosis (DVT).
7. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure or myocardial infarction within 6 months at the
time of consent or any Class 3 (moderate) or 4 (severe) cardiac disease defined by the
New York Heart Association Classification
8. Significant screening electrocardiogram (ECG) abnormalities including left bundle
branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block,
bradycardia (< 50bpm), or QTc >500 msec.
9. Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.
10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel or ulcerative colitis, symptomatic
inflammatory bowel disease, or partial or complete bowel obstruction.
11. Major surgery or wound that has not fully healed within 4 weeks or vaccination with
live attenuated vaccines within 4 weeks of the first dose of study drugs.
12. Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist.
13. Requires treatment with strong Cytochrome P4503A (CYP3A) inhibitors.
14. All patients with central nervous system lymphoma.