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

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ClinicalTrials.gov Identifier: NCT04856215
Recruitment Status : Not yet recruiting
First Posted : April 23, 2021
Last Update Posted : April 23, 2021
Sponsor:
Information provided by (Responsible Party):
Great Ormond Street Hospital for Children NHS Foundation Trust

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.


Condition or disease Intervention/treatment Phase
Leukemia Drug: 90-Yttrium-labelled anti-CD66 monoclonal antibody Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: 90-Yttrium-labelled anti-CD66 monoclonal antibody

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

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.





Primary Outcome Measures :
  1. Disease response after [90Y]-labelled anti-CD66 monoclonal antibody [ Time Frame: through study completion, upto 2 years post study ]
    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.


Secondary Outcome Measures :
  1. Assessment of timing of myeloid and platelet engraftment after allogeneic hematopoietic stem cell transplantation. [ Time Frame: through study completion, upto 2 years post study ]
    Assessment of timing of myeloid and platelet engraftment after allogeneic hematopoietic stem cell transplantation.

  2. Assessment of chimerism on bone marrow and peripheral blood to confirm engraftment of donor origin. [ Time Frame: through study completion, upto 2 years post study ]
    Assessment of chimerism on bone marrow and peripheral blood to confirm engraftment of donor origin.

  3. Safety Outcome [ Time Frame: through study completion, upto 2 years post study ]
    Toxicity will be classified using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0.



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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04856215


Contacts
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Contact: Sponsor (0) 20 7905 2000 ext 2863 ctimp.safety@gosh.nhs.uk

Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
Investigators
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Principal Investigator: Robert Chiesa Great Ormond Street Hospital
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Responsible Party: Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04856215    
Other Study ID Numbers: 17WA58
First Posted: April 23, 2021    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Neoplasms by Histologic Type
Neoplasms
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs