Radioimmunotherapy Conditioning With 131I- Apamistamab for Allogeneic Transplant in Relapse/Refractory AML

This trial consists of a Phase 2 randomized dose optimization component and a Phase 3 randomized, controlled two-arm component. This is a multicenter, open-label, study of 131I-apamistamab, fludarabine and TBI, which will be compared to standard of care regimen prior to HSCT in the Phase 3 portion, in subjects, aged 18 years old or greater, with active, relapsed or refractory AML. Active, relapsed or refractory AML is defined as any one of the following: (1) primary induction failure (PIF) after 2 or more cycles of therapy, or (2) first early relapse after a remission duration of fewer than 6 months, or (3) relapse refractory to salvage combination therapy, or (4) second or subsequent relapse.

All subjects will undergo screening prior to randomization in the study. Screening will include collection of informed consent, physical examination, review of inclusion/exclusion criteria with associated testing, summarizing documented history of AML and any other malignant disease, and identification and medical clearance of an appropriate allogeneic hematopoietic stem cell (HSC) donor.

Subjects must have active R/R AML with 5-20% blasts in marrow, documented CD45 expression, ≥18 years of age, not suitable for a myeloablative conditioning regimen, Karnofsky ≥70, and a medically cleared 8/8 matched HSC donor. Key exclusions include \>20% marrow blasts, prior HSCT, prior maximal organ radiation, active CNS leukemia, significant cardiac disease, abnormal QTcF \>450 ms, uncontrolled infection, or active malignancy within 2 years