Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma

Inclusion Criteria:

* Age greater than or equal to 18 years.
* Histologically or cytologically confirmed diagnosis of MCL.
* Relapsed or refractory MCL patients who have received at least one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible.
* Presence of at least one lymph node evaluable or mass measurable for response.
* Eastern Cooperative Oncology Group Performance Status greater than 2.
* Platelets \> 75,000/μL and absolute neutrophils count (ANC) \> 1,000/μL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of \> 750/mm 3 is allowed)
* Normal renal function defined as serum creatinine less than 2.
* Recovery from any previous treatment therapy.
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
* All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
* Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
* Ability to understand, and willingness to sign, a written informed consent document.
* Able to take aspirin (81 or 325 mg) daily as prophylactic anti-coagulation (patients intolerant to ASA may use low molecular weight heparin).
* Normal organ and bone marrow function parameter:

Laboratory tests Required value WBC \>3000/μL\* Absolute neutrophils count \>1,000/μL\* Platelets \>75,000/μL Total bilirubin \< 1.5Within normal institutional limits AST (SGOT) and ALT (SGPT) \<3 x institutional upper limit of normal Creatinine or creatinine clearance \<1.5 within normal institutional limits \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated by Cockcroft-Gault formula)

Exclusion Criteria:

* Concomitant use of warfarin or other Vit K antagonists
* Central nervous system (CNS) involvement by lymphoma at time of enrollment.
* Other medical conditions that would potentially interfere with patient participation in this trial.
* A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless for other tumor type patient was treated with curative intent at least 2 years previously.)
* Known human immunodeficiency virus (HIV-1) infection or chronic hepatitis B, or C (Hep B serology positive without active infection will be eligible)
* Active, clinically serious infection \> CTCAE grade 2. Patients may be eligible upon resolution of the infection.
* Major surgery or significant traumatic injury within 28 days of the first dose of study drug.
* Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of MCL within 21 days of starting treatment or 5 half life times (whatever is shorter)
* Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria:
* History of uncontrolled or symptomatic angina
* History of uncontrolled arrhythmias
* Myocardial infarction \< 6 months from study entry
* Uncontrolled or symptomatic congestive heart failure
* Ejection fraction below the institutional normal limit
* Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient
* Patients unwilling or unable to comply with the protocol.