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

NCT ID: NCT02633137

Last Updated: 2024-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-14
• Study Completion Date: 2023-11-07

Brief 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.

Detailed Description

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.

Conditions

Mantle Cell Lymphoma; Untreated

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy

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.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

R-CHOP

Intervention Type: DRUG

• 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

high-dose cytarabine (HIDAC)

Intervention Type: DRUG

Interventions

Lenalidomide

Intervention Type: DRUG

R-CHOP

• 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

Intervention Type: DRUG

high-dose cytarabine (HIDAC)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anita Kumar, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Commack

Commack, New York, United States

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

15-196

Identifier Type: -

Identifier Source: org_study_id