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

NCT07157514 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AIM-300
• Study Type: interventional
• Target: 306
• Locations: 0 countries
• Sites: N/A

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.

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

Keywords

Acute Myeloid Leukemia; Leukemia; Acute Myeloid; Acute Bone Marrow Cell Transplant; Transplant; Bone Marrow HCT; Refractory AML; Relapsed AML; I-131; Iomab; I131- Apamistamab; Iodine; Iodine-131; 131-I AML; Iomab-B; Radioimmunotherapy; Allogeneic Transplant; Radiotherapy; CD45; Anti-CD45 antibody; Apamistamab; Fludarabine; Bone Marrow Transplant; Radiolabeled antibody therapy; 131I -apamistamab

Outcome Measures

Primary Outcomes (3)

• Overall Survival (OS) -Phase 3

  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.

  Up to 5 years post-randomization

• Complete Remission (CR) at Day 28 Post-HSCT - Phase 2

  Number of subjects achieving CR by Day 28 (±3 days) post-HSCT, based on bone marrow assessment.

  Day 28 post-HSCT

• Incidence of Grade ≥4 Non-Hematologic Toxicity

  Number and proportion of subjects developing grade ≥4 non-hematologic toxicities as graded by NCI CTCAE v5.0.

  Up to 6 months post-HSCT

Secondary Outcomes (11)

• Event-Free Survival (EFS)

  Up to 5 years post-randomization

• Relapse-Free Survival (RFS)

  6 months post-HSCT and up to 5 years post-randomization

• Overall Response Rate (ORR)

  Day 28 post-HSCT and up to 12 months

• Duration of Remission (DOR)

  Up to 5 years post-randomization

• GvHD-Free Relapse-Free Survival (GRFS)

  Up to 5 years post-HSCT

Other Outcomes (7)

• Minimal Residual Disease (MRD) Negativity Rate

  Up to 12 months post-HSCT

• Adverse Events Related to Study Treatment

  Up to 5 years post-randomization

• Adverse Events of Special Interest

  Up to 5 years post-randomization

Study Arms (2)

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI

EXPERIMENTAL

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.

Drug: 131I-apamistamab; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation (TBI); Biological: Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Arm B: Active Comparator - Standard of Care Conditioning Regimen

ACTIVE COMPARATOR

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.

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Interventions

131I-apamistamab DRUG

Iodine-131 radiolabeled anti-CD45 monoclonal antibody (apamistamab). Administered IV as a dosimetric dose followed by treatment dose.

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI

Fludarabine DRUG

Fludarabine phosphate, 30 mg/m² IV daily on Days -6 through -2.

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI; Arm B: Active Comparator - Standard of Care Conditioning Regimen

Cyclophosphamide DRUG

Cyclophosphamide

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI; Arm B: Active Comparator - Standard of Care Conditioning Regimen

Total Body Irradiation (TBI) RADIATION

TBI, 200 cGy on Day -1 prior to HSCT.

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI

Allogeneic Hematopoietic Stem Cell Transplant (HSCT) BIOLOGICAL

Unmodified, G-CSF-mobilized donor stem cells infused on Day 0.

Arm A: Experimental: I131-apamistamab + Fludarabine + TBI; Arm B: Active Comparator - Standard of Care Conditioning Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Positive human anti-mouse antibody (HAMA) at screening.
• \>20% leukemic blasts in marrow.
• Prior radiation to maximally tolerated levels of any critical organ.
• Active CNS leukemia (blasts in CSF or CNS chloromas).
• Prior allogeneic or autologous HSCT.
• Candidates suitable for myeloablative conditioning.
• 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
• QTcF \>450 ms after correction of electrolytes (unless paced rhythm or investigator deems eligible; cardiology consult optional).
• Positive HIV, HBV, or HCV test (exceptions: vaccinated HBV, or positive hepatitis markers with adequate organ function).
• Active, uncontrolled infection.
• Acute promyelocytic leukemia (t\[15;17\]).
• 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
• Inability to tolerate diagnostic or therapeutic procedures, particularly radiation isolation.
• Received anti-leukemic therapy within 14 days prior to randomization (hydroxyurea allowed up to day of 131I-apamistamab).

Sponsors & Collaborators

• Actinium Pharmaceuticals: lead

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia

Interventions

fludarabine; Cyclophosphamide; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Central Study Contacts

Madhuri Vusirikala, MD

CONTACT

347-814-2268; mvusirikala@actiniumpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Adaptive, seamless Phase 2/3 design including Phase 2 randomized dose optimization followed by a Phase 3 randomized, controlled two-arm comparison of 131I-apamistamab conditioning versus control regimen.

Study Record Dates

• First Submitted: August 28, 2025
• First Posted: September 5, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2034
• Last Updated: September 10, 2025

Record last verified: 2025-09