Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research HIV Working Group

Abstract

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute–sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute–sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need.

Survival after diffuse large B‐cell lymphoma among children, adolescents, and young adults in California, 2001–2014: A population‐based study

“…We did not observe increased incidence of infection‐related deaths among HIV patients who received rituximab. These relevant findings reinforce the need to enroll HIV patients in prospective clinical trials and carefully consider the use of rituximab on the front‐line treatment of HIV‐related DLBCL patients.…”

Successful anti‐CD19 CAR T‐cell therapy in HIV‐infected patients with refractory high‐grade B‐cell lymphoma

“…2,3 There are several potential concerns that distinguish an HIV-infected patient from a patient without HIV being considered for CAR T-cell therapy. [12][13][14] Although much remains to be learned regarding CAR T-cell therapy in patients with refractory hematologic malignancies, with or without HIV infection, the cases presented herein demonstrate that patients with chemotherapy-refractory, highgrade, B-cell lymphoma can successfully undergo autologous CAR T-cell manufacturing, and subsequently can safely tolerate CAR T-cell therapy and achieve a durable complete remission. We do know that, in general, patients with HIV-associated malignancies can tolerate full-dose cancer therapy as appropriate for their HIV-uninfected counterparts.…”

An Analysis of Recent FDA Oncology Scientific Publications

“…FDA oncology staff are in a unique position to articulate important research questions based on review work across cancer types and product classes and have access to oncology clinical trial data submitted by multiple sponsors for meta‐analyses and data to study patterns of regulatory submissions over time . Recent FDA oncology publications have addressed a variety of regulatory science topics, including the following: Describing new methods to design clinical trials for regulatory submissions such as master protocols , patient‐reported outcome tools , expansion cohorts , and tumor‐agnostic drug development . Exploring clinical trial endpoints . Investigating approaches to ensure that clinical trials are representative of the general population such as expanding eligibility criteria , understanding representation of diverse populations , and using real world data (e.g., electronic health record data) to inform regulatory actions . …”