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.

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.

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.