Clinical Trial Example
One example of a clinical trial run through the BCRP is our phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT — a trial supported
by the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP 9204, NCT01822509). We hypothesized that immune checkpoint blockade with the CTLA-4 blocking antibody ipilimumab could restore antitumor reactivity through a graft-versus-tumor
effect. A total of 28 patients were enrolled and received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients
who had clinical benefit.
In the six patients treated in the 3 mg/kg dose cohort, minimal efficacy or safety issues were observed, so an additional 22 patients were recruited and received a dose of 10 mg/kg. In that group, 5 (23 percent) patients had a complete response, 2 (9
percent) had a partial response, and 6 (27 percent) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia (example in Figure 1) and 1 patient with the myelodysplastic syndrome. Four patients
had a durable response for more than 1 year. Immune-related adverse events, including one death, were observed in 6 patients (21 percent), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients
(14 percent). Our correlative laboratory studies found that the clinical responses were associated with in situ infiltration of cytotoxic CD8+ T cells (Figure 2), decreased activation of regulatory T cells, and expansion of subpopulations of effector
T cells in the blood.
We concluded that ipilimumab is a feasible treatment option for patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. We published these results in the New England Journal of Medicine (Davids et al., N Engl J Med, 2016), and recently gave an oral presentation to provide updated data at the 2017 ASH Annual Meeting (Davids et al., abstract 275). We subsequently expanded the trial to evaluate the safety and efficacy of the PD-1 blocking antibody nivolumab in this same patient population, and accrual is ongoing.
BCRP sites were major contributors to accrual of this trial, which allowed us to efficiently recruit a geographically diverse array of patients and allow several patients to enroll who were unable to travel to Boston. In addition to helping with patient
access and speed of accrual, the ability to draw on the BCRP sites to increase the patient samples available for correlative laboratory studies has been another important advantage of opening trials in the consortium. The high-quality data produced
over a relatively short period of time through BCRP studies are already helping to shift the paradigm of clinical trial collaboration in hematologic malignancies.
We welcome inquiries about BCRP participation and trials for this continuously growing and evolving effort.