Lymphoma
Developing a prospective lymphoma clinical cohort in Malawi
(PI, Dr.Yuri Fedoriw, Enrollment Complete)
The Kamuzu Central Hospital Lymphoma Study is a prospective observational cohort of pathologically confirmed lymphoproliferative disorders diagnosed and treated at KCH in Lilongwe, Malawi. The study has been funded by the National Cancer Institute. Initiated in 2013, the target enrollment for the study is 1200 patients. The current PI is Dr. Yuri Fedoriw, while Dr. Matthew Painschab serves as the head supervisor for the study in Malawi. The primary purpose of this study is to develop a large prospective longitudinal lymphoma cohort at KCH. Subjects with confirmed hematologic malignancies treated according to local standards of care will be actively followed for five years after diagnosis to assess clinical outcomes. All study laboratories and procedures which are being performed are consistent with international standards of care. Even without study implementation, all procedures may be undergone by patients at KCH, and there is no ‘new’ intervention being provided by the study which is currently absent in Malawi. However, current clinical and laboratory assessments of lymphoma patients at KCH over time are typically highly inconsistent and incomplete by international standards, as a result of scarcity of resources and personnel. It is therefore hoped that the study will provide greater standardization and uniformity in the longitudinal characterization of patients with lymphoma at KCH, and allow data collected to be used for clinical as well as research purposes, as such data from sub-Saharan Africa are lacking and can be tremendously informative. The primary objective of the study is to develop a prospective registry of lymphoma patients in Malawi who are comprehensively and longitudinally characterized with respect to clinical, laboratory, and histopathologic features while receiving care according to local standards. We aim to study prognostic impact of baseline characteristcs, HIV, treatment, and immunologic background including T cell function and underlying lymphoma tumor immune microenvironment. Secondary objectives include characterization of non-lymphoma diagnoses among patients in Malawi referred for suspected lymphoma, understanding key genetic patterns in lymphoma specimens in Malawi in order to gain insights into lymphomagenesis in this setting and identify therapeutic targets for optimized treatment, and examination of correlations between clinical and laboratory findings among patients with suspected lymphoma and final histopathologic diagnoses, in order to develop optimal diagnostic algorithms in settings of limited diagnostic pathology.
Quality of life and physical function among cancer survivors in Malawi
(PI, Stephen Kimani, Kate Westmoreland, Enrollment Complete)
The purpose of this study is to compare quality of life and physical function impairment among breast cancer and lymphoma survivors in Malawi to age- and sex-matched controls by employing a sequential, mixed-methods design involving qualitative (phase 1) followed by quantitative (phase 2) evaluations, using the PROMIS survey and objective performance-based measures. The qualitative phase will recruit 30 cancer survivors (at least 10 breast cancer and 10 lymphoma survivors). The quantitative phase will recruit 100 cancer survivors (50 breast cancer and 50 lymphoma survivors) and 100 age- and sex-matched, healthy controls without cancer. Recruitment and study assessments will take place at the Kamuzu Central Hospital in Malawi. Primary objectives: To qualitatively examine unmet needs pertaining to QOL and physical function among breast cancer and lymphoma survivors in Malawi. To compare QOL and physical function impairment among breast cancer and lymphoma survivors in Malawi to age- and sex-matched controls, using the PROMIS survey and objective performance-based measures. Secondary objectives: To compare QOL and physical function impairment between breast cancer and lymphoma survivors in Malawi. To compare QOL and physical function impairment by HIV status among breast cancer and lymphoma survivors in Malawi.
Development and implementation of a symptom toolkit to improve the quality of life of adolescent and young adult oncology patients while receiving chemotherapy in Malawi
(PI, Alyssa Tilly, Kate Westmoreland, Closed)
We propose to implement a symptom toolkit in Malawi to assess its effectiveness in managing patient symptoms, with the overall goals of improving quality of life and successful treatment completion. We will use patient-reported outcome (PRO) measures, which have been increasingly used in resource-rich settings to estimate disease and treatment effects on patients’ mental, physical, and social health-related quality of life (HRQoL). PRO measures are innovative in that they are reported directly by patients, without clinicians or nurses as intermediaries, and are considered the methodologic gold standard in resource-rich settings. The Patient Reported Outcomes Measurement Information System 25-item pediatric short form (PROMIS-25) assesses six HRQoL domains—mobility, anxiety, depression, fatigue, peer relationships, and pain interference. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) assesses15 core symptom domains include: abdominal pain, constipation, diarrhea, oral mucositis, nausea, vomiting, fatigue, pain, anorexia, headache, peripheral sensory neuropathy, anxiety, depression, insomnia, and cough. In our previous work, the pediatric PROMIS-25 instrument to measure HRQoL and the PRO-CTCAE instrument have been translated into Chichewa, Malawi’s national language, and culturally validated for local use. The implementation of these cutting-edge PRO measures in Malawi will allow the holistic and comprehensive assessment of symptomatic adverse events, HRQoL, and utility of the symptom toolkit. This is similar to ongoing efforts in resource rich countries and is particularly important in SSA, where healthcare delivery is historically patriarchal, and shared decision making between patients and providers is not the cultural norm. Objectives 1) Demonstrate the feasibility of a symptom management toolkit among AYA Lymphoma patients in Malawi. 2) Measure the impact of the symptom toolkit on HRQoL using the Chichewa Pediatric PROMIS-25 Profile and on symptom management using the Chichewa Pediatric PRO-CTCAE.
Etiology and outcomes of neutropenic fever in patients receiving high-risk chemotherapy in Malawi
(PI, Dr.Matthew Painschab, Closed)
In this 1-year, pilot, prospective cohort study, the plan was to enroll 100 patients receiving chemotherapy at KCH who are at high risk for neutropenic fever. They were to collect temperature measurements daily in their home and report back to care if they develop a temperature ≥ 38 Celsius. When fever develops, we would systematically collect a comprehensive infectious workup in order to identify the causes of fever. Patients would simultaneously be treated according to a standard-of-care fever protocol and would be followed for 90 days to assess clinical outcomes. Any patient with a positive culture would need to have their antibiotics appropriately tailored to culture data and would have follow up cultures collected until culture sterilization. Clinical outcomes would also be measured after 90 days of follow up. To date there has been no comparable large-scale effort to evaluate the causes of neutropenic fever among cancer patients in SSA, nor have there been published attempts to standardize the management of neutropenic fever in SSA. A better understanding of neutropenic fever and the common bacterial infections among cancer patients in SSA is needed for safer cytotoxic therapy escalation, ultimately leading to improved cancer-specific mortality and morbidity. By defining the spectrum and resistance of bacterial infections during neutropenic fever in cancer treatment in Malawi we can develop better prophylaxis and treatment plans for cancer populations across SSA. Our results will help prioritize antibacterial agents for inclusion in cancer program formularies, and guide development of febrile neutropenia clinical management algorithms for SSA settings.The primary objective was to define the frequency, spectrum and antibiotic susceptibility of bloodstream bacterial infections in patients receiving high-risk chemotherapy in Malawi, as well as the blood culture sterilization rates and survival of bacteremic cancer patients receiving appropriate local management. Secondary objectives include assessing the rate, causes and 90-day mortality rate of febrile neutropenia among high-risk cancer patients initiating chemotherapy in Malawi. In addition, we explored differences in the spectrum of invasive bacteria and clinical outcomes between subpopulations, such as HIV+ versus HIV-, hematologic versus non-hematologic cancers, and different chemotherapy regimens.
Rituximab Plus CHOP Chemotherapy clinical trial
(PI, Dr.Matthew Painschab, Closed)
Diffuse large B-cell lymphoma (DLBC) is the most common Non-Hodgkin lymphoma (NHL) subtype among HIV-infected and HIV-uninfected individuals. In the developed world, the standard of care (SOC) treatment for DLBCL is 6 cycles of CHOP with the addition of the targeted agent rituximab (R-CHOP). Rituximab was approved in the US in 1997 for treatment of NHL, and has been associated with a 10-15% absolute survival increase for patients with DLBCL when added to CHOP chemotherapy, with little additional toxicity even when applied to elderly and HIV-infected patients
The central hypothesis of this trial is that rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is safe among HIV-infected and HIV-uninfected diffuse large B-cell lymphoma (DLBCL) patients in Malawi, a setting with high infectious burden and limited supportive care including typically absent hematopoietic growth factors.
The primary objective of the study is to estimate the proportion of DLBCL patients receiving R-CHOP who experience NCI grade 3 or 4 non-hematologic toxicities and the proportion who experience treatment-related death over a course of six cycles. The secondary objectives include estimating the proportion of DLBCL patients by HIV status receiving R-CHOP who experience grade 3 or 4 non-hematologic toxicities over a course of six cycles; assess the achievable dose intensity for R- CHOP administered among DLBCL patients in Malawi with and without HIV infection; estimate PFS, OS, and CR rates for R-CHOP administered among DLBCL patients in Malawi overall, and with and without HIV infection; assess 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; and perform cost-effectiveness modeling for rituximab plus CHOP chemotherapy administered for six cycles among DLBCL patients in Malawi, using locally derived clinical trial and cost data.
Randomized, Phase II Trial of CHOP vs. Oral Chemotherapy with Concomitant Antiretroviral Therapy in Patients with HIV-associated Lymphoma in Sub-Saharan Africa
(Clincal Lead, Dr.Bongani Kaimila, Closed)
Approximately 10% of the world population lives in SSA, but the region is home to approximately 68% of the world population living with HIV. As the AIDS pandemic advances, the burden of related neoplastic disease is increasing in developing nations3,4. While under-developed cancer registries in SSA bar a definitive statement being made regarding increases in incidence and prevalence in Africa, it is felt that AIDS-Related Non-Hodgkin’s Lymphoma (AR-NHL) has rising incidence in this setting. The most comprehensive accounting of newly diagnosed NHL remains limited; between 2004 and 2008 only 51 HIV-infected patients were identified. Although CHOP chemotherapy was administered to approximately two-thirds of all patients, the estimated median survival, even among HIV-seronegative individuals, was less than 1 year and the authors found no evidence that receipt of chemotherapy improved survival. Although the available data on the performance of CHOP in HIV+ patients at AIDS Malignancy Clinical Trials Consortium sites in sub-Saharan Africa are too scant to draw firm conclusions, what little data are available suggest that there are factors that may limit CHOP’s optimal activity in resource-constrained settings. Additionally, studies of cytotoxic systemic therapy for AIDS-associated and other virus-associated tumors in similar settings report mortality rates ranging between 20-66% and the median survival duration for AIDS-related Burkitt’s lymphoma is 15 weeks. Prospective studies are needed to identify factors that have led to poorer than expected outcomes in NHL to standard CHOP-based approaches in resource-constrained settings and to determine whether these factors can be overcome. The study’s primary objective is to compare the efficacy of standard CHOP and an oral chemotherapy regimen for HIV-associated DLBCL in SSA with respect to overall survival (OS). Secondary objectives are to compare the objective response rate, progression free survival, and safety and tolerance of persons randomized to CHOP and oral chemotherapy.
Related Publications
A prospective description of HIV-associated multicentric Castleman disease in Malawi.
Discovering primary effusion lymphoma in Malawi.
How I treat Burkitt lymphoma in children, adolescents, and young adults in sub-Saharan Africa.
Plasmablastic Lymphoma in Malawi.
Lymphoma and pathology in Sub-Saharan Africa: current approaches and future directions.