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

Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02633137
• Other study ID #: 15-196
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2015
• Est. completion date: November 7, 2023

Study information

• Verified date: November 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 7, 2023
• Est. primary completion date: November 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Untreated

Intervention

Drug:
• Lenalidomide

• 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
• high-dose cytarabine (HIDAC)

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	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 Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year progression-free survival (PFS)	acceptable 3-yr PFS as 75% or higher, and unacceptable rate as 60% or lower.	3 years

External Links

•   Memorial Sloan Kettering Cancer Center