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

ConditionsAcute LeukemiaMyeloid LeukemiaAcute Myelogenous LeukemiaAcute Myeloid LeukemiaAcute Myeloid Leukemia, in RelapseMyelogenous LeukemiaMyelogenous Leukemia, AcuteMyelogenous Leukemia in RelapseTransplant-Related DisorderAllogeneic DiseaseRefractory AML
Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorActinium Pharmaceuticals

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Have active, relapsed, or refractory AML with ≥5% and ≤20% blasts in the marrow.

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

Documented CD45 expression by leukemic cells via flow cytometry.

≥18 years of age and not suitable for myeloablative conditioning regimen.

Disqualifiers

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).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 131I-apamistamab

    Drug

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

  • Fludarabine

    Drug

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

  • Cyclophosphamide

    Drug

    Cyclophosphamide

  • Total Body Irradiation (TBI)

    Radiation

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

  • Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

    Biological/Vaccine

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

Treatment groups

306 Participants
are divided into 2 treatment groups
Group A: Arm A: Experimental: I131-apamistamab + Fludarabine + TBIExperimental treatment 5 interventions
Group B: Arm B: Active Comparator - Standard of Care Conditioning RegimenActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 5 years post-randomization
2

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.

Time frame
Day 28 post-HSCT
3

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.

Time frame
Up to 6 months post-HSCT

Secondary outcomes

1

Event-Free Survival (EFS)

Time from randomization to relapse, treatment failure, or death from any cause, whichever occurs first.

Time frame
Up to 5 years post-randomization
2

Relapse-Free Survival (RFS)

Probability of being alive without previous relapse of disease among subjects who achieve a post-transplant CR or CRi.

Time frame
6 months post-HSCT and up to 5 years post-randomization
3

Overall Response Rate (ORR)

Proportion of subjects achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following transplant

Time frame
Day 28 post-HSCT and up to 12 months
4

Duration of Remission (DOR)

Time from first documented CR or CRi until relapse or death from any cause.

Time frame
Up to 5 years post-randomization

Other outcomes

1

Minimal Residual Disease (MRD) Negativity Rate

Proportion of subjects achieving MRD negativity by multiparameter flow cytometry among those with CR/CRi.

Time frame
Up to 12 months post-HSCT
2

Adverse Events Related to Study Treatment

Number and proportion of subjects of adverse events due to study treatment, summarized by severity.

Time frame
Up to 5 years post-randomization
3

Adverse Events of Special Interest

Number and proportion of subjects of adverse events of special interest, summarized by severity.

Time frame
Up to 5 years post-randomization
4

Rates of Engraftment and Graft Failure

Rate evaluation of number of subjects achieving ≥95% donor cell engraftment or graft failure by Day 100 post-HSCT

Time frame
Up to Day 100 post-HSCT

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Actinium Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: