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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Sequential Chemotherapy and Lenalidomide Followed by Rituximab and Lenalidomide Maintenance for Untreated Mantle Cell Lymphoma: A Phase II Study

Conditions
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Mantle Cell Lymphoma, Untreated

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: R-CHOP
* Drug: high-dose cytarabine (HIDAC)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br>Lenalidomide + R-CHOP x 4 cycles R-HiDAC x 2 cycles R-Len maintenance x 6 months. Patients will be followed on active follow up for three years after completion of therapy. After the active followup period, survival, relapse, and new anti-lymphoma therapy information will be collected via telephone calls, patient medical records, and/or clinic visits approximately every 6 months until death, loss to follow up or consent withdrawal, whichever comes first. | Drug: Lenalidomide<br> <br> Drug: R-CHOP<br>* Rituximab 375 mg/m^2 IVPB with premedications Day 1 Cyclophosphamide 750 mg/m^2 IVPB Day 1 Doxorubicin 50 mg/m^2 IVP Day 1 Vincristine 1.4 mg/m^2 IVP (capped at 2 mg) Day 1 Prednisone 100 mg PO Daily on Days 1-5 or 2-6<br>Drug: high-dose cytarabine (HIDAC)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progression-free survival (PFS) | acceptable 3-yr PFS as 75% or higher, and unacceptable rate as 60% or lower. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenalidomide, 15-196