sequential chemotherapy and lenalidomide followed by rituximab and lenalidomide maintenance for untreated mantle cell lymphoma

Conditions: Mantle Cell Lymphoma; Untreated

Summary: the purpose of this study is to find out what effects, good and/or bad, the treatment including 1) lenalidomide-rchop, 2) r-hidac, and 3) lenalidomide-rituximab maintenance has on the participant and their 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.

Eligibility criteria:
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.

Keywords: lenalidomide 15-196