VR-CAP in the First-line Treatment for Patients With Marginal Zone Lymphoma

Sponsor

Henan Cancer Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04433156

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

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 VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Marginal Zone Lymphoma	Drug: Bortezomib Drug: Rituximab Drug: Epirubicin Drug: Cyclophosphamide Drug: Prednisone	Phase 2

Detailed Description

Marginal zone lymphoma (MZL) is a relatively common group of non-Hodgkin's lymphoma (NHL). The incidence rate is only inferior to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Currently, NCCN guidelines recommend same treatment plan of FL like R-CHOP as the primary treatment for MZL. However, due to the great difference in cell origin and biological characteristics between FL and MZL, some patients can not achieve complete remission or relapse quickly after standard first-line treatment. A number of phase II clinical studies have evaluated the good efficacy of rituximab combined with chemotherapy in the treatment of MZL. Previous studies have shown that NF-κB signaling pathway is in abnormal activation state in MZL. Bortezomib, a proteasome inhibitor targeting NF-κB pathway, has a promising therapeutic prospect in relapsed and refractory MZL. The goal of our trial is to assess the efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone 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 VR-CAP in the First-line Treatment for Patients With Marginal Zone Lymphoma

Actual Study Start Date :

Apr 22, 2020

Anticipated Primary Completion Date :

Apr 22, 2022

Anticipated Study Completion Date :

Apr 22, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VR-CAP Rituximab, 375 mg/m2, Intravenous administration on day 0, Bortezomib, 1.3 mg/m2 hypodermic injection on day 1 and 4, combined with regimen: Cyclophosphamide, Epirubicin, and Prednisone: repeated every 3 weeks, up to 6 cycles.	Drug: Bortezomib 1.3 mg/m2, hypodermic injection on day 1 and day 4 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Bortezomib Injection Drug: Rituximab 375 mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: RiTUXimab Injection Drug: Epirubicin 70 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Epirubicin hydrochloride Drug: Cyclophosphamide 750 mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Other Names: Cyclophosphamide Injection Drug: Prednisone 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles Other Names: Prednisone Oral Product

Arm

Intervention/Treatment

Experimental: VR-CAP

Rituximab, 375 mg/m2, Intravenous administration on day 0, Bortezomib, 1.3 mg/m2 hypodermic injection on day 1 and 4, combined with regimen: Cyclophosphamide, Epirubicin, and Prednisone: repeated every 3 weeks, up to 6 cycles.

Drug: Bortezomib

1.3 mg/m2, hypodermic injection on day 1 and day 4 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

Bortezomib Injection

Drug: Rituximab

375 mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease after 2/4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Other Names:

RiTUXimab Injection

Drug: Epirubicin

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

Other Names:

Epirubicin hydrochloride

Drug: Cyclophosphamide

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

Other Names:

Cyclophosphamide Injection

Drug: Prednisone

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

Other Names:

Prednisone Oral Product

Outcome Measures

Primary Outcome Measures

2-year progression-free survival [from the beginning day of the first cycle (each cycle is 21 days) 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 beginning day of the first cycle (each cycle is 21 days) 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)
overall survival [from the beginning day of the first cycle (each cycle is 21 days) of treatment to the date of death from any cause, assessed up to 5 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 beginning day of the first cycle (each cycle is 21 days) of treatment to 6 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 marginal zone lymphoma
No receiving chemotherapy before enrollment
Indications for treatment: 1) symptoms related to tumor; 2) end-organ function damage;

large mass; 4) continuous or rapid progress of disease; 5) patient's willingness

Having at least one measurable lesions
World health organization-Eastern Cooperative Oncology Group Performance tatus (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 central nervous system lymphoma
World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG) ≥2
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
Active tuberculosis. Patients suspected of active TB need to be examined for chest X-ray, sputum and clinical symptoms and signs
HIV-positive, AIDS patients and untreated active hepatitis（HBV/HBV and HCV）
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