90Y-labelled Anti-CD66 ab in Childhood High Risk Leukaemia

NCT04856215 | Unknown Phase 2 DMC

• 1 other identifier: 17WA58
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

Children affected by high risk or relapsed/refractory leukaemia have a poor prognosis, with an increased risk of relapse. These patients generally need treatment intensification and a bone marrow transplantation (BMT). Nevertheless, with conventional treatent the risk of relapse after transplant remains high. Radioimmunotherapy provides a way to deliver high dose irradiation to the bone marrow (where leukaemia resides), while sparing normal organs and tissues from its toxicity.This can be achieved by linking a radioactive molecule (Yttrium90) to an antibody that, once infused in the blood, targets marrow/leukemic cells.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• Disease response after [90Y]-labelled anti-CD66 monoclonal antibody

  recovery of normal hematopoiesis in the bone marrow, with blasts \< 5% of lymphoid/myeloid cells and lack of evidence for residual leukemia using any informative cytogenetic/molecular marker. The number and proportion of patients who have a response will be provided in each cohort.

  through study completion, upto 2 years post study

Secondary Outcomes (3)

• Assessment of timing of myeloid and platelet engraftment after allogeneic hematopoietic stem cell transplantation.

  through study completion, upto 2 years post study

• Assessment of chimerism on bone marrow and peripheral blood to confirm engraftment of donor origin.

  through study completion, upto 2 years post study

• Safety Outcome

  through study completion, upto 2 years post study

Study Arms (1)

90-Yttrium-labelled anti-CD66 monoclonal antibody

EXPERIMENTAL

The medicinal product consists of the murine IgG1 anti-CD66 monoclonal antibody radio-labelled with 111In for imaging and dosimetry and with 90Y for therapy. Dosage indications The \[111In\]-labeled anti-CD66 monoclonal antibody (MAb) will be given at an infused activity of 100MBq/sqm between 1-4 weeks before the therapeutic dose of radiolabelled antibody. \[90Y\]-yttrium-labeled anti-CD66 MAb will be given as a single infusion on day - 14 prior to transplant. \[90Y\]-yttrium labelled anti-CD66 MAb will be given to target an absorbed dose to the bone marrow of 45 Gy +/- 10%. The maximum dose to be delivered to the liver and the kidneys is 15 Gy and 10 Gy, respectively.

Drug: 90-Yttrium-labelled anti-CD66 monoclonal antibody

Interventions

90-Yttrium-labelled anti-CD66 monoclonal antibody DRUG

The Investigational Medicinal Product (IMP) consist of 1) 111Indium- and 2) 90Yttrium-labelled anti-CD66 (BW250/183) monoclonal antibody. The anti-CD66 is a murine IgG1 monoclonal antibody originally developed as an in vivo leucocyte and bone marrow imaging agent (Boßlet 1985, Thomsen 1991). BW 250/183 anti-CD66 is a murine IgG1 kappa monoclonal antibody, originally produced as an anti-CEA antibody. The batch of antibodies required for treatment will be radiolabelled by Royal Free Hospital radiology team with Indium 111 and Y90 for patient.

90-Yttrium-labelled anti-CD66 monoclonal antibody

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• be ≥ 0.5 year old and ≤ 18 years old;
• 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;
• have a Karnofsky Performance Status ≥ 50 or Lansky Performance Status ≥ 30;
• provide signed, written informed consent from parent or guardian;
• be able to comply with study procedures and follow-up examinations;
• have adequate cardiac function (irrespective of concomitant cardio-vascular treatment) at PI/CI discretion;
• have adequate organ function (as indicated by Table 5) within 30 days prior to 111In infusion;
• 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;
• be negative for human-anti-murine antibodies (HAMA).

You may not qualify if:

• patients who are positive for human anti-murine antibodies (HAMA);
• patients with compromised organ function within 30 days prior to 111In infusion;
• patients with isolated CNS disease relapse\*;
• patients with an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment;
• 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\*\*.
• patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study;
• patients with extensive chronic graft versus host disease (GVHD);
• patients with unstable cardio-vascular disease. -

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead

Study Sites (2)

Great Ormond Street Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

University College London Hospital NHS Trust

London, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert Chiesa

  Great Ormond Street Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sponsor

CONTACT

(0) 20 7905 2000; ctimp.safety@gosh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 23, 2021
• Study Start: September 29, 2023
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: October 3, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)