Analysis of Factors Influencing Enrollment Success in Hematology Malignancy Cancer Clinical Trials (2008-2023)

Introduction:

Despite the importance of clinical trials in developing treatments to improve survival and quality of life in cancer patients (pts), enrollment in cancer trials faces significant challenges. Approximately 20% of cancer clinical trials fail due to insufficient pt enrollment, and 18% of phase I-III trials are ‘slow-enrolling’: enrolling fewer than two participants per year (Tang C et al., Clin Can Res, 2017). This study investigates the factors influencing enrollment success rates in hematology malignancy cancer trials, aiming to provide insights for improving future trial enrollment.

Methods:

In this cross sectional study we included interventional clinical trials with clear enrollment targets and actual enrollment data for adults (age≥18 years) acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) including myelofibrosis (MF), essential thrombocythemia (ET), polycythemia vera (PV), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), chronic myelomonocytic leukemias (CMML), Hodgkin’s disease (HD), non-Hodgkin’s lymphoma (NHL) and myeloma from clinicaltrials.gov between 2008 to 2023. (data was extracted using R package “ctrdata” (5) at cutoff date of 7/10/2024) Enrollment success rate (ESR) was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. Trial completion date after 12/31/2023 and non-interventional studies were excluded. The association of trial characteristics with enrollment success was evaluated via univariate analyses, using the chi-square test for categorical variables and the Kruskal- Wallis test for continuous variables with a significance threshold set at a p-value of <0.05.

Results:

A total of 2273 trials of leukemia, lymphoma, and myeloma were included: 423 of myeloma (18.61%), 216 of AML (9.50%), 122 of NHL (5.37%), 113 of MDS (4.97%), 110 of CLL (4.84%), 74 of MPN (3.26%), 843 of mixed lymphoid malignancy (37.09%), 242 of mixed myeloid malignancy (10.65%), and 130 of mixed myeloid lymphoid malignancy (5.72%). The overall ESR was 48.48% (1102/2273).

From 2008 to 2014, the ESRs were all greater than 50%, but from 2015 to 2022, the ESRs were all ≤50% (p<0.0001). Breakdown of ESR by phase was as follows: 52.5% in phase 4 (21/40), 70.95% in phase 3 (210/296), 40% in phase 2/phase 3 (6/15), 48.37% in phase 2 (549/1135), 41.77% in phase 1/phase 2 (175/419), 35.83% in phase 1 (86/240), and 42.86% in early phase 1 (3/7). (p<0.0001)

60.42% in industry-sponsored studies (600/993), 56.41% in network-sponsored (clinical trial networks, research collaborators, multi-center consortia) studies (22/39), 38.71% in NIH-sponsored studies (48/124), and 38.15% in other sponsors (academic institutions, non-profit organizations, individual researchers, government agencies excluding NIH) (380/996) had successful enrollment. (p<0.0001)

56.5% of parallel studies (400/708), 56.52% of crossover studies (13/23), 46.19% of single group studies (570/1234), 36.46% of sequential studies (66/181), and 16.67% of factorial studies (1/6) had successful enrollment. (p= <0.0001)

48.22% of studies with 1 primary endpoint had successful enrollment (665/1379), 48.51% of studies with 2 primary endpoints (211/435), and 51.48% of studies with 3 or more primary endpoints (174/338) (p=0.570). The median number of secondary endpoints for successful enrollment were 5, whereas for unsuccessful enrollments were 4. (p= <0.0001).

The median number of institutions at which a trial was open for successful enrollment was 6 and for unsuccessful enrollment was 1. Overall, the median number of clinical trial centers at which the studies were open were 2 (p<0.0001).

Conclusion:

In this largest analysis of its kind in hematological malignancy clinical trials, we show that ESR varies significantly based on trial phase, sponsor type, study design, and geographical distribution, with higher ESR observed in phase 3 trials, industry-sponsored studies, parallel study designs, and trials conducted across multiple countries. These factors need to be considered in future clinical trials to ensure high ESR by optimizing trial designs that caters to the indicated population across multiple institutions or countries.