Rituximab, Lenalidomide, and Bortezomib in Mantle Cell Lymphoma

Exclusion Criteria

• •1. Patient has \>1.5 x ULN total bilirubin.
• •2. Peripheral neuropathy ≥ CTCAE grade 2.
• •3. Relapsed or refractory patients who have received more than one prior therapy.
• •4. Pregnant or breastfeeding females. (Lactating females must agree not to breastfeed while taking lenalidomide.)
• •5. Female patients who have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
• •6. Thrombolic or embolic events (such as a cerebrovascular accident, including transient ischemic attacks) within the past 6 months.
• •7. Pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within 28 days of the first dose of study drug.
• •8. Any other hemorrhage/bleeding event ≥ CTCAE grade 3 ≤ 28 days of the first dose of study drug
• •9. Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• •10. Central nervous system (CNS) involvement by lymphoma at time of enrollment.
• •11. Other medical conditions or psychiatric illness that would potentially interfere with patient participation in this trial.
• •12. A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least 2 years previously.
• •13. Previous evidence of hypersensitivity to bortezomib, boron, mannitol, thalidomide, (and development of erythema nodosum if characterized by a desquamating rash), or rituximab (true anaphylaxis, not a rituximab-infusion reaction).
• •14. Known human immunodeficiency virus (HIV) infection or chronic hepatitis A, B, or C. Patients who are HIV positive or who are positive for chronic hepatitis A, B, or C will be excluded due to increased risk for bone marrow suppression and other toxicities.
• •15. Active, clinically serious infection \> CTCAE grade 2. Patients may be eligible upon resolution of the infection.
• •16. Evidence or history of bleeding diathesis or coagulopathy.
• •17. Major surgery, open biopsy, or significant traumatic injury within 28 days of the first dose of study drug.
• •18. Use of any other standard chemotherapy, radiation therapy, or experimental drug for the treatment of MCL within 28 days of starting treatment.
• •19. Any condition that impairs a patient's ability to swallow whole pills. Impairment of gastrointestinal function (GI) or GI disease that may significantly alter the absorption of lenalidomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• •20. Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria or any of the following:
• •* History of uncontrolled or symptomatic angina
• •* History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
• •* Myocardial infarction \< 6 months from study entry
• •* Uncontrolled or symptomatic congestive heart failure
• •* Ejection fraction below the institutional normal limit
• •* Electrocardiographic evidence of acute ischemia or active conduction system
• •* Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient
• •* Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• •21. Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 or diastolic BP \> 100mm Hg) or uncontrolled cardiac arrhythmias.
• •22. Any prior use of lenalidomide.