ACCELERATE: An Efficient and Innovative Natural History Study Addressing Unmet Needs in Castleman Disease

Project Summary/Abstract:
Castleman disease (CD) describes a group of rare and poorly understood hematologic disorders that share
characteristic histopathologic alterations, lymphadenopathy, and systemic inflammation but vary in etiology,
symptomatology, treatments, and outcomes. Approximately 2,000 individuals of all ages are diagnosed with CD
each year in the US. Unicentric CD (UCD) involves one region of enlarged lymph nodes and typically milder
inflammatory symptoms; the three currently-recognized subtypes of multicentric CD (MCD) result from different
etiologies but involve progressive episodes of systemic inflammatory symptoms and life-threatening cytokine-
driven multi-organ dysfunction, such as the liver, kidneys, and bone marrow. The underlying mechanisms and
therapeutic targets are not well understood. While various treatments are often tried for CD, systematic
evaluations of these treatments have not been performed, the optimal treatments for each subtype are not
known, and biomarkers to identify patients likely to respond to certain treatments are needed. New treatment
approaches are also needed, but no validated, patient-centric treatment response criteria or biomarkers exist to
consistently evaluate promising treatment approaches in clinical trials. Further, clinical data had not been
centralized and no evidence-based diagnostic or treatment guidelines existed until recently.
To address these barriers, we established an international longitudinal natural history study of CD in 2016
through a 5-year collaborative partnership between the Castleman Disease Collaborative Network, Janssen
Pharmaceuticals, and the University of Pennsylvania (lead institution). Developed by a team of physicians,
researchers, and patients, ACCELERATE utilizes an innovative patient-powered study design whereby CD
patients in the US and globally self-enroll online and our study team obtains and systematically extracts complete
medical record data into a central database. The use of common data standards, rigorous data extraction
protocols, and expert adjudication of each case ensure that the data is of high quality and interpretability. We
have enrolled over 500 CD patients and collected extensive, longitudinal data on approximately one-half that
have been leveraged to characterize the spectrum of CD, support the development of evidence-based treatment
guidelines, and advance translational research.
Despite these advances, significant unmet needs remain for the majority of CD patients who do not have
an effective FDA-approved therapy. Unfortunately, our 5-year funded study has ended. We are seeking funding
to leverage the data collected from our 5-year collaborative partnership, build upon infrastructure from this multi-
stakeholder collaboration, and continue enrollment and data collection to identify clinically-meaningful patient
subtypes, clinical outcome measures, and novel treatment approaches. Our proposed studies have the potential
to transform care for CD patients, overcome barriers to therapeutic product development, and establish a model
for rare disease natural history studies.

Grant Number: 5R01FD007632-04
NIH Institute/Center: FDA
Principal Investigator: Joshua Brandstadter