Challenges of HIV Lymphoma Clinical Trials in Africa: Lessons From the AIDS Malignancy Consortium 068 Study

Robert M. Strother, University of Otago, Christchurch, New Zealand.
Satish Gopal, Center for Global Health, National Cancer Institute, Rockville, MD.
Meg Wirth, The Emmes Corporation, Callaway, MD.
Amy Chadburn, Weill Cornell Medical College, New York, NY.
Ariela Noy, Memorial Sloan Kettering Cancer Center, New York, NY.
Ethel Cesarman, Weill Cornell Medical College, New York, NY.
Jeannette Y. Lee, University of Arkansas for Medical Sciences, Little Rock, AR.
Scot C. Remick, Maine Medical Center, Portland, ME, and Tufts University, Boston, MA.
Naftali Busakhala, Moi Teaching and Referral Hospital, Eldoret, Kenya.
Bongani Kaimila, University of North Carolina Project-Malawi, Lilongwe, Malawi.
Elson Mberi, University of Zimbabwe, Harare, Zimbabwe.
Ntokozo Ndlovu, University of Zimbabwe, Harare, Zimbabwe.
Abrahams Omoding, Uganda Cancer Institute, Kampala, Uganda.
Susan E. Krown, AIDS Malignancy Consortium, New York, NY.


The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.