Targeted radioimmunotherapy for children with high-risk leukemia

90Yttrium-labelled Anti-CD66 Monoclonal Antibody as Part of a Reduced Toxicity Conditioning Regimen Prior to Allogeneic Haematopoietic Stem Cell Transplantation: an Open Label, Phase II Study in Children and Adolescents With High Risk Leukaemia

This study is testing a new targeted radiation treatment for children with high-risk leukemia to see if it can help them before they undergo a bone marrow transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 6 Months to 18 Years
• Sex: All
• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (London and 1 other locations)
• Trial ID: NCT04856215 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of a 90Yttrium-labelled anti-CD66 monoclonal antibody in children aged 0.5 to 18 years with high-risk or relapsed leukemia. The study builds on previous findings that demonstrated the treatment's tolerability and minimal side effects in a smaller cohort. Participants will receive targeted radiotherapy prior to bone marrow transplantation, with follow-up assessments conducted for 12 months post-treatment to monitor outcomes. The goal is to improve treatment strategies for children who have a poor prognosis and high risk of relapse.

Who should consider this trial

Good fit: Ideal candidates include children aged 0.5 to 18 years with high-risk or relapsed leukemia who are not eligible for higher curative therapies.

Not a fit: Patients with leukemia who are eligible for alternative therapies with higher curative potential may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in children with high-risk leukemia after bone marrow transplantation.

How similar studies have performed: Previous studies have shown promising results with targeted radioimmunotherapy approaches, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. An underlying hematological malignancy including:

   a) relapse of AML after allogeneic hematopoietic stem cell transplantation; b) relapse of ALL after allogeneic hematopoietic stem cell transplantation; c) relapse of JMML after allogeneic hematopoietic stem cell transplantation; e) refractory ALL; f) refractory AML; g) high risk infant ALL;
2. be ≥ 0.5 year old and ≤ 18 years old;
3. must not be eligible for therapy of higher curative potential. Where an alternative therapy has been shown to prolong survival in an analogous population, this should be offered to the patient prior to discussing this study;
4. have a Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
5. provide signed, written informed consent from parent or guardian;
6. be able to comply with study procedures and follow-up examinations;
7. have adequate cardiac function (irrespective of concomitant cardio-vascular treatment) at PI/CI discretion;
8. have adequate organ function (as indicated by Table 5) within 30 days prior to 111In infusion;
9. patients who have received any other chemotherapy within the previous 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrolment;
10. be negative for human-anti-murine antibodies (HAMA).

Exclusion Criteria:

1. patients who are positive for human anti-murine antibodies (HAMA);
2. patients with compromised organ function within 30 days prior to 111In infusion;
3. patients with isolated CNS disease relapse\*;
4. patients with an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment;
5. Pregnant or breast-feeding females are excluded due to potential risks of foetal adverse events of an investigational agent. Pregnancy tests must be obtained prior to enrolment on this study for girls of reproductive potential. The need to commence pregnancy testing will be at the discretion of the treating physician to facilitate taking in to account factors such as precocious puberty, endocrine status and medications which can affect pubertal status. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Sexual Abstinence is an acceptable method of birth control\*\*.
6. patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
7. patients with extensive chronic graft versus host disease (GVHD);
8. patients with unstable cardio-vascular disease. -

Where this trial is running

London and 1 other locations

• Great Ormond Street Hospital NHS Foundation Trust — London, United Kingdom (Recruiting)
• University College London Hospital NHS Trust — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Principal investigator: Robert Chiesa — Great Ormond Street Hospital
• Study coordinator: Sponsor

Conditions Leukemia