Sequential Chemotherapy and Lenalidomide Followed by Rituximab and Lenalidomide Maintenance for Untreated Mantle Cell Lymphoma

Patients will receive lenalidomide 15 mg orally daily on days 1-14 with standard-dose R-CHOP
(375 mg/m^2 intravenous rituximab, 750 mg/m2 intravenous cyclophosphamide, 50 mg/m^2
intravenous doxorubicin, and 1.4 mg/m2 intravenous vincristine on day 1, and 100 mg
prednisone days 1-5 or days 2-6) every 21 days for four cycles.

All patients will receive pegfilgrastim on day 2 of each cycle and aspirin 81 mg orally daily
for venous thromboembolism prophylaxis throughout the four cycles.

After four cycles of Len-RCHOP, the patients will undergo restaging PET/CT scans. Patients
with evidence of disease progression will be treated off study.

R-HIDAC After lenalidomide-RCHOP phase, patients without evidence of progressive disease will
receive rituximab 375 mg/m^2 day 1 and then patients will be admitted for high-dose
cytarabine (HIDAC). Recommended age-adjusted HIDAC doses are as follows: ≤65 years: 3 g/m2
every12 hours X 4 doses; 65-70 years: 2 g/m^2 every12 hours X 4 doses; >70 years: 1 g/m^2
every12 hours X 4 doses. Physician discretion will dictate the choice of HIDAC dose, ranging
from 1 g/m^2 - 3 g/m^2 every 12 hours X 4 doses.

Patients will receive two cycles of rituximab-HIDAC every 3 weeks. After two cycles of
R-HIDAC, the patients will undergo restaging PET/CT scans. Patients with evidence of disease
progression will be treated off study.

Len-Rituximab Maintenance After completion of induction chemotherapy with Len-RCHOP and
R-HIDAC, patients will begin maintenance phase with lenalidomide and rituximab for 6 months.
Lenalidomide will be administered at 15 mg orally daily on days 1-21 of a 28-day cycle for a
total of 6 cycles and rituximab maintenance every 8 weeks for a total of 3 treatments.

Inclusion Criteria:

- Previously untreated mantle cell lymphoma patients (at least clinical stage 2)

- Histologic diagnosis confirmed by MSKCC pathologist as mantle cell lymphoma

- Presence of evaluable disease

- Age ≥18 years KPS ≥ 70%

- Adequate organ function: ANC ≥1500 and platelet count ≥100,000, unless felt to be
secondary to underlying mantle cell lymphoma

- Renal function assessed by calculated creatinine clearance as follows:

- Cockcroft-Gault estimation of CrCl):

- Calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula. See
section below, "Dosing Regimen", regarding lenalidomide dose adjustment for
calculated creatinine clearance ≥30ml/min and < 60ml/min.

- Adequate hepatic function as determined by

- Total bilirubin <1.5X upper limit of normal (ULN) (unless known Gilbert syndrome)

- AST (SGOT) and ALT (SGPT) 3 x ULN

- 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.

- Each subject must sign an informed consent form indicating that he or she understand
the purpose of and procedures required for the study and are willing to participate.

- Short course systemic corticosteroids is permissible for disease control, improvement
of performance status or non-cancer indication if ≤ 10 days and must be discontinued
prior to study treatment.

Exclusion Criteria:

- Known central nervous system (CNS) lymphoma

- Uncontrolled or severe cardiovascular disease or left ventricular ejection fraction
<50% as determined by echocardiogram or MUGA.

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety or put the study
outcomes at undue risk.

- Pregnant or breast-feeding. Pre-menopausal patients must have a negative serum HCG
within 14 days of enrollment.

- Patients using ≥20 mg/day of prednisone (or steroid equivalent dose) for any chronic
medical condition

- Known seropositive, requiring anti-viral therapy, and with detectable viral load by
PCR for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C
virus (HCV).

- Known hypersensitivity to thalidomide or lenalidomide

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

- Patients planned for upfront consolidation with high-dose therapy and autologous stem
cell transplant.