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

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

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.

Study Overview

• Status: Completed
• Conditions: Mantle Cell Lymphoma; Untreated
• Intervention / Treatment: Drug: Lenalidomide; Drug: R-CHOP; Drug: high-dose cytarabine (HIDAC)

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Lenalidomide; 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; Drug: high-dose cytarabine (HIDAC)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Anita Kumar, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: December 14, 2015
• Primary Completion (Actual): November 7, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Lenalidomide; 15-196
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Cytarabine
• Other Study ID Numbers: 15-196