R-CHOP Combined With Lenalidomide in the First-line Treatment for Patients With Diffuse Large B Cell Lymphoma

Sponsor

Henan Cancer Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04214626

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of R-CHOP (Rituximab-Cyclophosphamide, Epirubicin, Vincristine and Prednisone) combined with lenalidomide in the first-line treatment for patients with medium to high risk/high risk diffuse large B cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Drug: Rituximab Drug: Lenalidomide Drug: Cyclophosphamide Drug: Epirubicin Drug: Vincristine Drug: Prednisone Drug: Methotrexate	Phase 2

Detailed Description

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Currently, R-CHOP is world-widely used in the first-line treatment for DLBCL. There are about one second of patients suffering relapse and drug resistance. Lenalidomide is an analog of thalidomide, the mechanism of anti-tumor action has not been fully elucidated. Lenalidomide has been proved to inhibit the proliferation of tumor cells in certain hematopoietic systems. At present, it has been approved for the treatment of multiple myeloma with good efficacy and safety. The goal of our trial is to assess the efficacy and safety of R-CHOP combined with lenalidomide in the first-line treatment for patients with medium to high risk/high risk diffuse large B cell lymphoma.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single Arm, Multi-center, Phase II Clinical Trial of R-CHOP Combined With Lenalidomide in the First-line Treatment for Patients With Medium to High Risk/High Risk Diffuse Large B Cell Lymphoma

Actual Study Start Date :

Jan 2, 2020

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP regimen Combined With Lenalidomide Induction Chemotherapy: Rituximab, 375mg/m2, Intravenous administration on day 0, Lenalidomide, 25mg oral administration on day 1 to 10, combined with regimen：CHOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone): repeated every 3 weeks, up to 6 cycles. PS: Methotrexate, 3mg/m2, Intravenous administration on day 3 of each 3-week cycle, from 2 to 5 cycles for patients with high recurrence risk of the central nervous system. Maintenance Treatment: Rituximab, 375mg/m2, Intravenous administration on day 0 repeated every 4 weeks, up to 2 cycles; Lenalidomide, 10mg oral administration on day 1 to 21 repeated every 4 weeks, up to 12 cycles.	Drug: Rituximab Induction Chemotherapy: 375mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment: Rituximab, 375mg/m2, Intravenous administration on day 0 repeated every 4 weeks until disease progression or unacceptable toxicity develops, up to 2 cycles. Other Names: RiTUXimab Injection Drug: Lenalidomide Induction Chemotherapy: 25mg, oral administration on day 1 to 10 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment: 10mg oral administration on day 1 to 21 repeated every 4 weeks until disease progression or unacceptable toxicity develops, up to 12 cycles. Other Names: Lenalidomide capsule Drug: Cyclophosphamide Induction Chemotherapy: 750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Cyclophosphamide Injection Drug: Epirubicin Induction Chemotherapy: 70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Epirubicin hydrochloride Drug: Vincristine Induction Chemotherapy: 1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Vincristine Injection Drug: Prednisone Induction Chemotherapy: 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Prednisone Oral Product Drug: Methotrexate Induction Chemotherapy: 3mg/m2, Intravenous administration on day 3 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, from 2 to 5 cycles for patients with high recurrence risk of the central nervous system. Other Names: Methotrexate Injectable Solution

Arm

Intervention/Treatment

Experimental: R-CHOP regimen Combined With Lenalidomide

Induction Chemotherapy: Rituximab, 375mg/m2, Intravenous administration on day 0, Lenalidomide, 25mg oral administration on day 1 to 10, combined with regimen：CHOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone): repeated every 3 weeks, up to 6 cycles. PS: Methotrexate, 3mg/m2, Intravenous administration on day 3 of each 3-week cycle, from 2 to 5 cycles for patients with high recurrence risk of the central nervous system. Maintenance Treatment: Rituximab, 375mg/m2, Intravenous administration on day 0 repeated every 4 weeks, up to 2 cycles; Lenalidomide, 10mg oral administration on day 1 to 21 repeated every 4 weeks, up to 12 cycles.

Drug: Rituximab

Induction Chemotherapy: 375mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment: Rituximab, 375mg/m2, Intravenous administration on day 0 repeated every 4 weeks until disease progression or unacceptable toxicity develops, up to 2 cycles.

Other Names:

RiTUXimab Injection

Drug: Lenalidomide

Induction Chemotherapy: 25mg, oral administration on day 1 to 10 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment: 10mg oral administration on day 1 to 21 repeated every 4 weeks until disease progression or unacceptable toxicity develops, up to 12 cycles.

Other Names:

Lenalidomide capsule

Drug: Cyclophosphamide

Induction Chemotherapy: 750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

Cyclophosphamide Injection

Drug: Epirubicin

Induction Chemotherapy: 70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

Epirubicin hydrochloride

Drug: Vincristine

Induction Chemotherapy: 1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

Vincristine Injection

Drug: Prednisone

Induction Chemotherapy: 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

Prednisone Oral Product

Drug: Methotrexate

Induction Chemotherapy: 3mg/m2, Intravenous administration on day 3 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, from 2 to 5 cycles for patients with high recurrence risk of the central nervous system.

Other Names:

Methotrexate Injectable Solution

Outcome Measures

Primary Outcome Measures

2-year progression-free survival [from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment]
the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first

Secondary Outcome Measures

objective response rate [every 6 weeks from the day of the first cycle of induction chemotherapy treatment and every 8 weeks from the day of the first cycle of maintenance treatment to 18 months after last patient's enrollment]
the total proportion of patients with complete response (CR) and partial response (PR)
2-year overall survival [from date of the first cycle of treatment to the date of death from any cause, assessed up to 2 years]
from date of first day of treatment to the date of death by any cause
incidence and relationship with study drugs of grade 3-4 adverse events [from the date of the first cycle of treatment to 18 months after last patient's enrollment]
the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18 to 70 years old (including 18 and 70)
Diagnosed as diffuse large B cell lymphoma
Subjects must be untreated (medium to high risk/high risk: International Prognostic Index (IPI) score 3-5, aaIPI score 2-3 or NCCN-IPI score≥ 4/ Immunohistochemical staining of double expression (BCL2 ≥ 70% and C-MYC ≥ 40%) or P53 protein mutation positive ≥ 50%)
No receiving chemotherapy before enrollment
Having at least one measurable lesions
World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1
Life expectancy no less than 3 months
enough main organ function
Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study
Agreeing to sign the written informed consents

Exclusion Criteria:

Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike
Diagnosed as grey-zone lymphoma
Diagnosed as central nervous system lymphoma
Diagnosed as primary mediastinal large B-cell lymphoma
Diagnosed as CD20 negative diffuse large B-cell lymphoma
Other malignant tumor history or active malignant tumor need be treated
Serious surgery and trauma less than two weeks
Systemic therapy for serious acute/chronic infection
Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
Vaccination with live attenuated vaccine less than 4 weeks
HIV-positive, AIDS patients and untreated active hepatitis
Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
Patients with a history of mental illness
Researchers determine unsuited to participate in this trial