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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Single Arm, Multi-center, Phase II Clinical Trial of VR-CAP in the First-line Treatment for Patients With Marginal Zone Lymphoma

Conditions
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Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Rituximab
* Drug: Epirubicin
* Drug: Cyclophosphamide
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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; 3) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VR-CAP<br>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<br>* 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.<br>* Other names: Bortezomib Injection;Drug: Rituximab<br>* 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.<br>* Other names: RiTUXimab Injection;Drug: Epirubicin<br>* 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.<br>* Other names: Epirubicin hydrochloride;Drug: Cyclophosphamide<br>* 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.<br>* Other names: Cyclophosphamide Injection;Drug: Prednisone<br>* 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<br>* Other names: Prednisone Oral Product;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year progression-free survival | 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response (CR) and partial response (PR) | 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 | 
| overall survival | from date of first day of treatment to the date of death by any cause | 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 | 
| incidence and relationship with study drugs of grade 3-4 adverse events | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03 | from the beginning day of the first cycle (each cycle is 21 days) of treatment to 6 months after last patient's enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Marginal Zone Lymphoma, VR-CAP