An Independent Data Monitoring Committee has recommended the pivotal phase 3 SIERRA study continue as planned to full enrollment of 150 patients based on the findings from a pre-planned ad hoc interim analysis of the study.
An Independent Data Monitoring Committee has recommended the pivotal phase 3 SIERRA study continue as planned to full enrollment of 150 patients based on the findings from a pre-planned ad hoc interim analysis of the study, which is exploring outcomes of patients over the age of 55 with active relapsed/refractory acute myeloid leukemia (AML) receiving Iomab-B and a bone marrow transplant, Actinium Pharmaceuticals, Inc., announced in a press release.
SIERRA is currently over 75% enrolled and is the only randomized phase 3 study to offer a potentially curative bone marrow transplant as treatment of patients with active relapsed/refractory AML. The company has not received the unblinded primary and secondary end point efficacy data from the randomized, controlled study.
"We are encouraged by the Data Monitoring Committee’s recommendation to continue the SIERRA trial as planned and that there continues to be no safety concerns from the Iomab-B arm. All of us at Actinium are intensely focused on completing the final portion of patient enrollment in the SIERRA trial," said Mark Berger, MD, chief medical officer, Actinium.
The company performed a single ad hoc analysis in April 2020 consistent with the study’s design, and this allowed up to 2 ad hoc analyses between 70 and 110 patients. This analysis was exercised for a number of patients that represent less than two-thirds of the expected final recruitment. There was a minimal alpha spend resulting in a p-value threshold of 0.046 for the primary end point, which is durable CR of at least 180 days.
During the American Society of Hematology (ASH) 2020 Annual Meeting, findings for the first 75% of patients were highlighted in an oral presentation and showed a 100% rate of bone marrow transplant and engraftment in patients receiving a therapeutic dose of Iomab-B. A second oral presentation demonstrated lower rates of sepsis and sepsis-related grade ≥3 adverse events (AEs) were observed with the use of Iomab-B compared with findings in the control arm, in which patients receive physician’s choice of salvage therapies, including recently approved agents like venetoclax (Venclexta) who may proceed to bone marrow transplant if they achieve the required complete remission (CR).
In addition, the experimental arm had lower rates of serious AEs categories, which included sepsis, febrile neutropenia, mucositis, and 100-day non-relapse transplant-related mortality.
"The recent presentations at ASH highlight Iomab-B's value proposition to universally enable older patients with active relapsed or refractory AML to proceed to a potentially curative bone marrow transplant via a well-tolerated targeted conditioning regimen, which we believe will be a paradigm shift compared to current non-targeted chemotherapy regimens that restrict patient access to bone marrow transplant,” stated Berger. “While we believed there was potential for early stoppage of the trial as a result of this ad hoc analysis, we note that the hurdle rate for early stoppage, given the smaller number of patients representing less than two thirds of full enrollment, was much higher for the ad hoc than what is now required at the final analysis of 150 total patients. With the large difference in the number of patients advancing to bone marrow transplant with Iomab-B and those potentially evaluable for durable CR compared to the control arm through seventy-five percent of enrollment, we remain strongly optimistic about the ultimate success of SIERRA.”
Actinium announces successful pre-planned ad hoc interim analysis of phase 3 SIERRA trial. News Release. Actinium Pharmaceuticals, Inc. December 29, 2020. Accessed January 5, 2021. https://yhoo.it/3933CLg