A conditioning regimen consisting of of Iomab-B prior to a bone marrow transplant met the phase 3 SIERRA trial’s primary end point of durable complete remission compared with conventional care in elderly patients with relapsed or refractory acute myeloid leukemia.
Topline results from the phase 3 SIERRA trial (NCT02665065) indicated that Iomab-B, when used as a conditioning regimen before a bone marrow transplant, garnered promising responses vs conventional care in older patients with relapsed or refractory acute myeloid leukemia (AML), according to a press release from Actinium Pharmaceuticals.
The primary end point of durable complete remission (dCR) at 6 months following initial remission after a bone marrow transplant was met among patients receiving Iomab-B and was considered to be statistically significant (P <.0001). Investigators of the SIERRA trial noted that patients tolerated Iomab-B well, and stated that the safety profile was consistent with previous clinical data. Additional clinical data from the SIERRA trial will be shared by the end of the year, according to Sandesh Seth, chairman and chief executive officer at Actinium.
“We are excited that the randomized, controlled, multi-center, pivotal SIERRA trial has delivered these results for patients that need new treatment options,” Avinash Desai, MD, chief medical officer of Actinium, said in the press release. “Our goal is to increase access to [bone marrow transplant] and improve patient outcomes with Iomab-B, and these topline results move us in this direction given their statistical significance.”
Iomab-B is a targeted radiotherapy agent designed to improve patient access to possibly curative bone marrow transplant by depleting blood cancer and immune and bone marrow stem cells that express CD45. The regimen previously received orphan drug designation from the FDA for older patients diagnosed with AML.
The randomized, multi-center phase 3 SIERRA study compared Iomab-B plus bone marrow transplant with physician’s choice of salvage therapy in a population of 153 patients. Those who enrolled were randomly assigned to either receive Iomab-B in conjunction with a reduced intensity conditioning regimen before bone marrow transplant or investigator’s choice of salvage treatment, which included chemotherapy agents such as cytarabine and daunorubicin, as well as targeted agents such as a Bcl-2 inhibitor venetoclax (Venclexta), FLT3 inhibitors, and IDH 1/2 inhibitors; by utilizing over 20 agents and combinations, investigators were able to have the control arm reflect the real-world treatment paradigm. The trial enrolled patients across 24 leading transplant centers in the United States and Canada.
Secondary end points of the SIERRA trial include overall survival and event-free survival measured over a 5-year period.
Patients 55 years and older with active relapsed or refractory AML were eligible to enroll on the study. Additional inclusion criteria included having documented CD45 expression by leukemic cells via flow cytometry, a circulating blast count of less than 10,000/mm3, adequate hepatic function, a Karnofsky score of at least 70, and an expected survival of more than 60 days.
Patients were not able to enroll on the study if they had received prior maximally tolerated radiation doses to any critical normal organ or active leukemic central nervous system involvement. Patients were also not able to enroll if they previously received a hematopoietic stem cell transplant, had clinically significant cardiac disease, active serious infection uncontrolled by antibiotics or antifungals, acute promyelocytic leukemia and associated cytogenic translocation, and active malignancy within 2 years of study entry.
Actinium announces positive top-line results from pivotal phase 3 SIERRA trial of Iomab-B in patients with active relapsed or refractory acute myeloid leukemia. News release. Actinium Pharmaceuticals. October 31, 2022. Accessed November 1, 2022. http://bit.ly/3Dp3zsd