Inclusion Criteria

1. Documentation of Disease:

1. Histologically documented mantle cell lymphoma, with the following
immunophenotypic characteristics: cluster of differentiation (CD)5+, (CD)23-,
cyclin D1+; this may be from an initial diagnostic biopsy, or one obtained at
time of relapse

2. Institutional flow cytometry or immunohistochemistry must confirm CD5 antigen
expression, lack of CD23 antigen expression, and expression of cyclin D1.

2. Prior Treatment - Patients must have prior treatment with at least one regimen, which
may have been single agent or multi-agent, and consisted of traditional cytotoxic
agents and/or biologic agents. Patient must not have received prior idelalisib or
lenalidomide therapy. Patient must have progressive disease or refractory disease
following the initial regimen(s). Refractory disease will be defined as stable
disease (SD) or progressive disease (PD) as best response to prior therapy, or
complete response (CR) or partial response (PR) as initial response followed by
disease progression within 6 months. Prior autologous, but not allogeneic, stem cell
transplant is allowed. No corticosteroids within two weeks prior to study, except for
maintenance therapy for a non-malignant disease. Maintenance therapy dose may not
exceed 20 mg/day prednisone or equivalent.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status - Patients must have
ECOG performance status of 0-2.

4. Measurable Disease must be present either on imaging studies. Non-measurable disease
alone is not acceptable. Any tumor mass > 1 cm by computed tomography (CT), magnetic
resonance imaging (MRI), or conventional radiograph is acceptable. Lesions that are
considered non-measurable include the following:

1. Bone lesions (lesions, if present, should be noted)

2. Ascites

3. Pleural/pericardial effusion

4. Lymphangitis cutis/pulmonis

5. Bone marrow (involvement by non-Hodgkin lymphoma should be noted)

5. Central Nervous System (CNS) Involvement - Patients must have no known CNS
involvement by lymphoma.

6. Human Immunodeficiency Virus (HIV) Infection - Patients with HIV infection are
eligible, provided they meet the following:

1. CD4+ cell count > 350/mm3

2. Treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50
copies/mm3

3. No history of Acquired Immune Deficiency Syndrome (AIDS)-defining conditions or
other HIV related illness

4. No concurrent zidovudine or stavudine because of overlapping toxicities with
protocol therapy

5. Patients with known HIV positivity must have CD4 assessment and viral load at
baseline and every 6 months while on study.

7. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing. 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 registration.
Further, they must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control: one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
starting lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must
agree to use a latex condom during sexual contact with a FCBP, even if they have had
a successful vasectomy. A FCBP is a sexually mature woman who: 1) has not undergone a
hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal
for at least 24 consecutive months (i.e., has had menses at any time preceding 24
consecutive months).

8. Deep Vein Thrombosis/Pulmonary Embolism (DVT/PE) - Patients with a recent history
(within 3 months of study entry) of DVT/PE are not eligible. Patients with a distant
history (greater than 3 months before study entry) of DVT/PE are eligible, but must
receive either prophylactic aspirin or low molecular weight heparin, unless
contraindicated.

9. Congestive Heart Failure - Patients must have no New York Heart Association (NYHA)
Class III or Class IV congestive heart failure at study entry.

10. Myocardial Infarction - Patients must have no myocardial infarction within 6 months
prior to study entry.

11. Hepatitis - Patients must not have known positivity for hepatitis B, as evidenced by
+ HBsAg or +anti-HBc, and must not have known history of hepatitis C.

12. Patients must be ≥ 18 years of age.

13. Cytochrome P450 3A4 (CYP3A4) Strong Inducers and Inhibitors - Patients must not be on
strong CYP3A4 inhibitors and/or inducers.

1. The following strong inhibitors are prohibited: indinavir, nelfinavir,
ritonavir, clarithromycin, itraconazole, ketoconazole,nefazodone

2. The following strong inducers are prohibited: carbamazepine, phenobarbital,
phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort, troglitazone

14. Required Initial Laboratory Values:

1. ANC ≥ 1,000/µL, ≥ 500/µL if marrow involvement

2. Platelets ≥ 75,000/µL

3. Creatinine ≤ 1.5 x ULN, and estimated creatinine clearance ≥ 60 mL/min
(patients on dialysis not eligible), unless attributable to non-Hodgkin lymphoma

4. Total bilirubin ≤ 2 x ULN, unless attributable to non-Hodgkin lymphoma or
Gilbert's disease