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

Not Applicable

Not yet recruiting

• Conditions: Acute Leukemia; Myelogenous Leukemia in Relapse; Myeloid Leukemia; Acute Myelogenous Leukemia; Acute Myeloid Leukemia; Allogeneic Disease; Acute Myeloid Leukemia, in Relapse; Myelogenous Leukemia; Myelogenous Leukemia, Acute; Transplant-Related Disorder
• Interventions: Drug: 131I-apamistamab; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Allogeneic Hematopoietic Stem Cell Transplant (HSCT); Radiation: Total Body Irradiation (TBI)

• Registration Number: NCT07157514
• Lead Sponsor: Actinium Pharmaceuticals

Brief 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

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-28
• Study First Submitted QC: 2025-08-28
• Last Update Submitted: 2025-08-28
• Study First Posted: 2025-09-05
• Last Update Posted: 2025-09-05
• Study Start: 2026-01-01
• Primary Completion: 2029-02
• Study Completion: 2034-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 306

Inclusion Criteria

1. Have active, relapsed, or refractory AML with ≥5% and ≤20% blasts in the marrow.
2. 2R/R AML is defined as one of the following: Primary induction failure after ≥2 cycles of therapy, first early relapse after remission <6 months, relapse refractory to salvage combination therapy or second or subsequent relapse
3. Documented CD45 expression by leukemic cells via flow cytometry.
4. ≥18 years of age and not suitable for myeloablative conditioning regimen.
5. Circulating blast count <10,000/mm³ (hydroxyurea allowed).
6. Calculated creatinine clearance (Cockcroft-Gault) >50 mL/min.
7. Adequate hepatic function: AST/ALT ≤2 × ULN; total bilirubin ≤1.5 × ULN (≤3 × ULN if due to underlying malignancy or Gilbert's).
8. Karnofsky performance score ≥70.
9. Expected survival >60 days.
10. Central venous catheter line in place before study treatment.
11. 8/8 HLA-matched related or unrelated donor (HLA-A, HLA-B, HLA-C, DRB1).
12. Women of childbearing potential must be surgically sterile or use acceptable contraception through 1-year post-transplant.
13. Men with partners of childbearing potential must be surgically sterile or use acceptable contraception through 12 weeks after last dose.
14. Able to understand procedures, provide informed consent, and comply with study requirements.

Exclusion Criteria

1. Positive human anti-mouse antibody (HAMA) at screening.
2. >20% leukemic blasts in marrow.
3. Prior radiation to maximally tolerated levels of any critical organ.
4. Active CNS leukemia (blasts in CSF or CNS chloromas).
5. Prior allogeneic or autologous HSCT.
6. Candidates suitable for myeloablative conditioning.
7. Clinically significant cardiac disease, including: NYHA Class III or IV heart failure, Clinically significant arrhythmias (ventricular tachycardia, ventricular fibrillation, Torsade de Pointes), Myocardial infarction with uncontrolled angina within 6 months, Clinically significant congestive heart failure or cardiomyopathy
8. QTcF >450 ms after correction of electrolytes (unless paced rhythm or investigator deems eligible; cardiology consult optional).
9. Positive HIV, HBV, or HCV test (exceptions: vaccinated HBV, or positive hepatitis markers with adequate organ function).
10. Active, uncontrolled infection.
11. Acute promyelocytic leukemia (t[15;17]).
12. Active malignancy within 2 years, except: Myelodysplastic syndrome, Treated non-melanoma skin cancer, Completely resected stage 0-1 melanoma (>1 year from resection), Carcinoma in situ or cervical intraepithelial neoplasia, Organ-confined prostate cancer without progression
13. Inability to tolerate diagnostic or therapeutic procedures, particularly radiation isolation.
14. Received anti-leukemic therapy within 14 days prior to randomization (hydroxyurea allowed up to day of 131I-apamistamab).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Experimental: I131-apamistamab + Fludarabine + TBI	131I-apamistamab	Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm A: Experimental: I131-apamistamab + Fludarabine + TBI	Fludarabine	Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm A: Experimental: I131-apamistamab + Fludarabine + TBI	Cyclophosphamide	Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm B: Active Comparator - Standard of Care Conditioning Regimen	Allogeneic Hematopoietic Stem Cell Transplant (HSCT)	Participants receive standard of care conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0 GvHD prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm A: Experimental: I131-apamistamab + Fludarabine + TBI	Total Body Irradiation (TBI)	Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm B: Active Comparator - Standard of Care Conditioning Regimen	Fludarabine	Participants receive standard of care conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0 GvHD prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm A: Experimental: I131-apamistamab + Fludarabine + TBI	Allogeneic Hematopoietic Stem Cell Transplant (HSCT)	Participants receive a dosimetric dose and then a treatment dose of I131-apamistamab (at the marrow dose selected in Phase 2), followed by fludarabine 30 mg/m² IV daily on Days -6 through -2 and total body irradiation (TBI) 200 cGy on Day -1 prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0. Graft-versus-host disease (GvHD) prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.
Arm B: Active Comparator - Standard of Care Conditioning Regimen	Cyclophosphamide	Participants receive standard of care conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HSCT) on Day 0 GvHD prophylaxis per investigator's choice: * Post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4) + tacrolimus + mycophenolate mofetil, OR * Low-dose methotrexate + tacrolimus.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) -Phase 3	Up to 5 years post-randomization	Defined as time from randomization to death from any cause. Subjects without documented death at the time of analysis will be censored at the date of last known contact.
Complete Remission (CR) at Day 28 Post-HSCT - Phase 2	Day 28 post-HSCT	Number of subjects achieving CR by Day 28 (±3 days) post-HSCT, based on bone marrow assessment.
Incidence of Grade ≥4 Non-Hematologic Toxicity	Up to 6 months post-HSCT	Number and proportion of subjects developing grade ≥4 non-hematologic toxicities as graded by NCI CTCAE v5.0.

Secondary Outcome Measures

Name	Time	Method
Relapse-Free Survival (RFS)	6 months post-HSCT	Probability of being alive without relapse at 180 days among subjects achieving CR/CRi.
Overall Response Rate (ORR)	Day 28 post-HSCT and up to 12 months	Proportion of subjects achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following transplant
Duration of Remission (DOR)	Up to 5 years post-randomization	Time from first documented CR or CRi until relapse or death from any cause.
Incidence of Acute and Chronic GvHD	6 months post-HSCT	Number and proportion of subjects developing acute or chronic GvHD, summarized by severity.
Event-Free Survival (EFS)	Up to 5 years post-randomization	Time from randomization to relapse, treatment failure, or death from any cause, whichever occurs first.
GvHD-Free Relapse-Free Survival (GRFS)	Up to 5 years post-HSCT	Composite endpoint defined as time from HSCT to first event of grade III-IV acute GvHD, chronic GvHD requiring systemic therapy, relapse, or death.
Survival Rate at One and Two Years Post-Transplant	1 year and 2 years post-HSCT	Proportion of subjects alive at one year and two years following HSCT.
Overall Survival	Up to 2 years post-enrollment	Time from enrollment to death from any cause.
Engraftment	Day 100 post-HSCT	Number of subjects achieving ≥95% donor cell engraftment by Day 100 post-HSCT.
Time to Engraftment	Up to Day 100 post-HSCT	Days from HSCT (Day 0) until subject reaches ≥95% donor cell engraftment.