Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers

Lin, Lilie L.; Lakomy, David S.; Chiao, Elizabeth Y.; Strother, Robert Matthew; Wirth, Meg; Cesarman, Ethel; Borok, Margaret; Busakhala, Naftali; Chibwesha, Carla J.; Chinula, Lameck; Ndlovu, Ntokozo; Orem, Jackson; Phipps, Warren; Sewram, Vikash; Vogt, Samantha L.; Sparano, Joseph A.; Mitsuyasu, Ronald T.; Krown, Susan E.; Gopal, Satish

doi:10.1200/go.20.00153

Cited by 14 publications

(9 citation statements)

References 70 publications

(68 reference statements)

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“…A network is likely to span all relevant epidemiological, political, and socioeconomic challenges in Africa, and is likely to be a springboard for effective north-south and south-south collaborations. The inclusion of people with HIV in the trial by Kimani and colleauges 4 -a population that is still excluded in many trials 7,8 in Africa-is a positive aspect of the trial design that should be carried forward in future oncology trials because HIV will continue to exacerbate cancer disparities between developed and developing countries.…”

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confidence: 99%

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Mbulaiteye

2021

The Lancet Global Health

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The global burdens of cancer incidence and mortality are increasing at an alarming pace, particularly on the African continent, 1 which is ill-equipped to monitor, respond to, and control these increases. Africa's share of global cancer mortality, which was estimated as 7•2% in 2020, is currently outpacing its share of cancer incidence, which was estimated as 5•7%. 1 This disparity is expected to continue worsening towards, and possibly beyond, 2040. 2 Although the reasons for these negative cancer statistics in Africa are manifold, they can be grouped into system factors (ie, weak economies, underdeveloped health-care infrastructures, and a low trained health-care worker-to-patient ratio); social factors (ie, barriers to treatment access and suspicion toward so-called western medicine); epidemiological factors (ie, demographic shifts in the population, a high prevalence of oncoviruses and HIV, and dynamic comorbidity profiles); and informational factors (ie, the shortage of reliable data to inform policy). 3 In The Lancet Global Health, Stephen Kimani and colleagues 4 report results of their study, which is a small but important step towards addressing the cancer burden in Africa. Given that patients with diffuse large B-cell lymphoma (DLBCL) in Malawi are unlikely to have access to the recommended first-line therapy of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy 5 under routine government programmes, the authors designed a clinical trial to investigate the feasibility, safety, and efficacy of R-CHOP in this population. The authors used a costeffective biosimilar to rituximab from India (known as Reditux; Dr Reddy's Laboratories, Hyderabad, Telangana, India). The study was done at one centre in Lilongwe in Malawi, and screened 76 patients, of whom 37 with confirmed DLBCL were eligible, enrolled, and given up to six cycles of R-CHOP. Of these 37 patients, 27 (83%) were HIV-positive with CD4 counts of more than 100 cells per µL. Baseline characteristics, including sex, median age, and stage of disease, were not significantly different between HIV-positive and HIV-negative patients.Despite a higher frequency of treatment delays in HIV-positive patients than HIV-negative patients, all

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confidence: 99%

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Mbulaiteye

2021

The Lancet Global Health

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“…The availability of cancer clinical trials reflects a country's clinical research capacity and is likely associated with the provision of evidence-based cancer care and improved patient outcomes. 11 Although countries in Africa account for a very small percentage of worldwide cancer clinical trials, 12 , 13 including 1,376 trials total and 444 active trials (Table 1 , Fig 1 , on the basis of data from ClinicalTrials.gov), the trials that have been performed have resulted in practice-changing insights. 14 - 16 These studies are particularly important given that, compared with patients in Europe and North America, patients in Africa respond to treatment differently because of cancer biology, 3 , 5 nutritional status, and HIV coinfection.…”

Section: Purpose and Methodsmentioning

confidence: 99%

Action for Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials—Is Africa the Answer? Report From a Satellite Session of the Accelerating Anti-Cancer Agent Development and Validation Workshop

Kizub

Manner

Graef

et al. 2022

JCO Global Oncology

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Patients of African ancestry are not well-represented in cancer clinical trials despite bearing a disproportionate share of mortality both in United States and Africa. We describe key stakeholder perspectives and priorities related to bringing early-stage cancer clinical trials to Africa and outline essential action steps. Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials—Is Africa the Answer? satellite session was organized at 2021 Accelerating Anti-Cancer Agent Development and Validation Workshop. Panelists included representatives of African Organization for Research and Training in Cancer, Uganda Cancer Institute, Uganda Women's Cancer Support Organization, BIO Ventures for Global Health, Bill & Melinda Gates Foundation, the US Food and Drug Administration, Nigeria's National Agency for Food and Drug Administration and Control, Bayer, and Genentech, with moderators from ASCO and American Cancer Society. Key discussion themes and resulting action steps were agreed upon by all participants. Panelists agreed that increasing diversity in cancer clinical trials by including African patients is key to ensuring novel drugs are safe and effective across populations. They underscored the importance of equity in clinical trial access for patients in Africa. Panelists discussed their values related to access and barriers to opening clinical trials in Africa and described innovative solutions from their work aimed at overcoming these obstacles. Multisectoral collaboration efforts that allow leveraging of limited resources and result in sustainable capacity building and mutually beneficial long-term partnerships were discussed as key to outlined action steps. The panel discussion resulted in valuable insights about key stakeholder values and priorities related to bringing early-stage clinical trials to Africa, as well as specific actions for each stakeholder group.

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“…A 2020 review by the AIDS Malignancy Consortium, which includes leaders of African clinical trial sites involved in the consortium, found no clinical trials actively enrolling patients with HIV-associated lymphoma in sub-Saharan Africa. 26 Additionally, a randomised clinical trial by the same consortium initiated in November, 2016, which aimed to compare an investigational oral regimen with CHOP in patients with HIV-associated DLBCL, was stopped after only seven patients in four sub-Saharan African countries (including Malawi) were enrolled over 2 years. 26,27 Before this trial, the only completed clinical trial focused on adults with lymphoma in sub-Saharan Africa evaluated an investigational oral regimen (lomustine, etoposide, cyclophosphamide, and procarbazine) in HIV-infected patients in Kenya and Uganda in 2001-05, before public sector ART was widely available.…”

Section: Table 2: Treatment Course and Toxic Effects In Patients With Diffuse Large B-cell Lymphoma Who Received R-chopmentioning

confidence: 99%

“…26 Additionally, a randomised clinical trial by the same consortium initiated in November, 2016, which aimed to compare an investigational oral regimen with CHOP in patients with HIV-associated DLBCL, was stopped after only seven patients in four sub-Saharan African countries (including Malawi) were enrolled over 2 years. 26,27 Before this trial, the only completed clinical trial focused on adults with lymphoma in sub-Saharan Africa evaluated an investigational oral regimen (lomustine, etoposide, cyclophosphamide, and procarbazine) in HIV-infected patients in Kenya and Uganda in 2001-05, before public sector ART was widely available. 22 Of 149 screened patients with HIV and lymphoma, 49 (33%) were ultimately given the investigational regimen, among whom median overall survival was 12•3 months.…”

Section: Table 2: Treatment Course and Toxic Effects In Patients With Diffuse Large B-cell Lymphoma Who Received R-chopmentioning

confidence: 99%

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

Kimani

Painschab

Kaimila

et al. 2021

The Lancet Global Health

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Background There are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi.Methods This prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18-60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0-2, a CD4 count of 100 cells per µL or higher (if HIVpositive), measurable disease by physical examination, an absolute neutrophil count of 1000 × 10⁹ cells per L or higher, a platelet count of 100 × 10⁹ platelets per L or higher, a serum creatinine concentration of 132•60 µmol/L or less, a total bilirubin concentration of 34•21 µmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², and vincristine 1•4 mg/m² (maximum 2 mg/m²), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710.

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Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers

Cited by 14 publications

References 70 publications

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Action for Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials—Is Africa the Answer? Report From a Satellite Session of the Accelerating Anti-Cancer Agent Development and Validation Workshop

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

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