Rituximab Plus CHOP Chemotherapy for Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to establish the safety of rituximab plus cyclophosphamide, doxorubicin, vincristine,prednisone (R-CHOP) in HIV-infected and HIV-uninfected diffuse large B-cell lymphoma (DLBCL) patients in Malawi.

Detailed Description
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The study is a single-center, non-randomized phase II clinical trial of R-CHOP for CD20-positive DLBCL, using the Indian generic biosimilar for rituximab, Reditux™. The investigators will enroll 40 adult patients age 18-60 years (20 HIV-infected with CD4 count ≥ 100 cells/µL, 20 HIV-uninfected) who will receive a maximum of 6-8 cycles of R-CHOP over 18-24 weeks. The primary goal of this study is to establish the safety of R-CHOP in the Malawi population. Secondary objectives of the study include estimates of complete response (CR) rates, progression-free survival (PFS), and overall survival (OS). In addition, quality of life, costs of care, study patient characteristics, clinical outcomes and other published data from the region will be collected and used to evaluate the cost-effectiveness of R-CHOP. If the investigators' study supports incorporating rituximab into treatment regimens in sub-Saharan Africa, this strategy can be examined in larger trials, and provide momentum to increase access to modern cancer medicines globally.

Official Title
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LCCC 1335: A Single-Arm Phase I/II Clinical Trial of Rituximab Plus CHOP Chemotherapy for Diffuse Large B-cell Lymphoma in Malawi

Conditions
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Diffuse Large B-cell Lymphoma, HIV

Intervention / Treatment
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* Drug: R-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained and signed. Age 18-60 years. ECOG performance status (PS) 0-2. Histologically confirmed CD20-positive DLBCL, any stage, bulky or nonbulky disease. No prior treatment for lymphoma. Willing to have documentation of HIV status. CD4 count ≥ 100 cells/µL if HIV-infected. Measurable disease by physical exam. Adequate bone marrow renal and hepatic function as evidenced by the following: Absolute neutrophil count (ANC) ≥ 1,000/µL Platelet count ≥ 100,000/µL Creatinine ≤ 1.5 mg/dL Total bilirubin ≤ 2 mg/dL (unless directly attributable to lymphoma) Able to understand and comply with protocol requirements for the entire length of the study. Willing to reside <50 kilometers from Kamuzu Central Hospital (KCH) until chemotherapy completion. Negative urine B-HCG in women of child-bearing potential within 7 days prior to start of treatment. Fertile patients must use effective contraception (condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during and for six months after completion of treatment. Exclusion Criteria Pregnant or nursing. Central nervous system (CNS) involvement by lymphoma (clinically or cytologically confirmed). Receiving other anti-cancer or investigational therapy during study treatment, apart from those agents specified in the study protocol. Known cardiac disease including any of the following: New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months prior to Day 1 History of stroke or transient ischemic attack within 6 months prior to Day 1 Second active malignancy requiring systemic therapy. Hepatitis B virus (HBV) surface-antigen positive unless receiving both tenofovir and lamivudine as part of antiretroviral therapy if HIV-infected. Other serious, ongoing, non-malignant disease or infection that would in the opinion of the site investigator compromise other protocol objectives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: R-CHOP<br>We will enroll 40 adult patients age 18-60 years (20 HIV-infected with CD4 count ≥ 100 cells/µL, 20 HIV-uninfected) who will receive a maximum of 6-8 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) over 18-24 weeks | Drug: R-CHOP<br>* maximum of 6-8 cycles of R-CHOP over 18-24 weeks<br>* Other names: Indian generic biosimilar for rituximab, Reditux™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of DLBCL patients receiving R-CHOP who experience NCI grade 3 or 4 non-hematologic toxicities | Safety will be assessed by grading toxicity events according to NCI Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAEv4) other than for hypersensitivity reactions to rituximab. Toxicities will be assessed, graded and documented by investigators at each clinic visit, and then tabulated. | 5 years | 
| Number of patients who experience treatment-related death over a course of six cycles |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of DLBCL patients by HIV status receiving R-CHOP who experience grade 3 or 4 non-hematologic toxicities over a course of six cycles |  | 5 years | 
| Number of patients receiving ≥ 90% of the prescribed doses of doxorubicin and cyclophosphamide, respectively among DLBCL patients in Malawi with HIV infection |  | 24 months | 
| Number of patients receiving ≥ 90% of the prescribed doses of doxorubicin and cyclophosphamide, respectively among DLBCL patients in Malawi without HIV infection |  | 24 months | 
| Number of patients with progression free survival with R-CHOP administered |  | 5 years | 
| Number of patients with overall survival with R-CHOP administered |  | 5 years | 
| Number of patients with complete response rates with R-CHOP administered |  | 24 months | 
| Number of years from treatment initiation until disease progression or death. | Questionnaire - health-related quality of life (via the EORTC QLQ-C30) among DLBCL patients in Malawi overall and with and without HIV infection receiving R-CHOP | 5 years | 
| Number of years gained after rituximab plus CHOP chemotherapy administered |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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single arm phase 2, safety and efficacy, R-CHOP