NCT07157514

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

An Adaptive, Operationally Seamless Phase II / III Study of 131I-apamistamab-Led Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia With Active Disease

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 306 (estimated)
• Sponsor: Actinium Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, open-label study in people aged 18 and older with relapsed or refractory acute myeloid leukemia. It has two parts. In Phase 2, we are testing three radiation dose levels of 131I-apamistamab combined with fludarabine and low-dose whole-body radiation before stem cell transplant to find the safest and most effective dose. In Phase 3, patients will be randomly assigned to receive either this treatment combination or a standard of care regimen before transplant. The main goal is to see if the new approach helps people live longer. Phase 2 will enroll about 60 people, and Phase 3 will enroll about 246 people.

Detailed description

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

Conditions

• Acute Leukemia
• Myeloid Leukemia
• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Acute Myeloid Leukemia, in Relapse
• Myelogenous Leukemia
• Myelogenous Leukemia, Acute
• Myelogenous Leukemia in Relapse
• Transplant-Related Disorder
• Allogeneic Disease
• Refractory AML

Interventions

Type	Name	Description
DRUG	131I-apamistamab	Iodine-131 radiolabeled anti-CD45 monoclonal antibody (apamistamab). Administered IV as a dosimetric dose followed by treatment dose.
DRUG	Fludarabine	Fludarabine phosphate, 30 mg/m² IV daily on Days -6 through -2.
DRUG	Cyclophosphamide	Cyclophosphamide
RADIATION	Total Body Irradiation (TBI)	TBI, 200 cGy on Day -1 prior to HSCT.
BIOLOGICAL	Allogeneic Hematopoietic Stem Cell Transplant (HSCT)	Unmodified, G-CSF-mobilized donor stem cells infused on Day 0.

Timeline

• Start date: 2026-01-01
• Primary completion: 2029-02-01
• Completion: 2034-02-01
• First posted: 2025-09-05
• Last updated: 2025-09-10

Regulatory

• FDA-regulated drug study