Rituximab Plus CHOP Chemotherapy for Diffuse Large B-cell Lymphoma

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

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.

Study Overview

• Status: Completed
• Conditions: HIV; Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: R-CHOP

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malawi
  • Lilongwe, Malawi
    • UNC Project, Lighthouse Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: R-CHOP; 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; maximum of 6-8 cycles of R-CHOP over 18-24 weeks; Other Names: Indian generic biosimilar for rituximab, Reditux™

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Fogarty International Center of the National Institute of Health

Publications and helpful links

General Publications

• Kimani S, Painschab MS, Kaimila B, Kasonkanji E, Zuze T, Tomoka T, Mulenga M, Nyasosela R, Chikasema M, Mtangwanika A, Chawinga M, Mhango W, Nicholas S, Chimzimu F, Kampani C, Krysiak R, Lilly A, Randall C, Seguin R, Westmoreland KD, Montgomery ND, Fedoriw Y, Gopal S. Safety and efficacy of rituximab in patients with diffuse large B-cell lymphoma in Malawi: a prospective, single-arm, non-randomised phase 1/2 clinical trial. Lancet Glob Health. 2021 Jul;9(7):e1008-e1016. doi: 10.1016/S2214-109X(21)00181-9. Epub 2021 May 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): July 22, 2021
• Study Completion (ACTUAL): July 22, 2022

Study Registration Dates

• First Submitted: January 17, 2016
• First Submitted That Met QC Criteria: January 20, 2016
• First Posted (ESTIMATE): January 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: R-CHOP; safety and efficacy; single arm phase 2
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: LCCC 1335; K01TW009488 (U.S. NIH Grant/Contract); R21CA180815 (NIH)