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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02633137

Collaborator

Celgene Corporation (Industry)

Enrollment

Locations

Arm

95.6

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma Untreated	Drug: Lenalidomide Drug: R-CHOP Drug: high-dose cytarabine (HIDAC)	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 14, 2015

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

3-year progression-free survival (PFS) [3 years]
acceptable 3-yr PFS as 75% or higher, and unacceptable rate as 60% or lower.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553