High risk relapsed or refractory leukaemia in childhood
Conditions
Interventions
Product Name: Indium-111-labelled Anti CD66 antibody
Pharmaceutical Form: Infusion
INN or Proposed INN: Indium-111 radiolabelled anti-CD66 monoclonal antibody (INN of Anti-CD66 Besilesomab)
Concentrat
Sponsors
Great Ormond Street Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria for admission in the study: 1) An underlying haematological malignancy including: a) isolated bone marrow relapse of AML after allogeneic haematopoietic stem cell transplantation; b) isolated bone marrow relapse of ALL after allogeneic haematopoietic stem cell transplantation; c) bone marrow relapse of JMML after allogeneic haematopoietic stem cell transplantation; d) refractory AML (5-20% blasts in BM) with/without expression of CD66 on blasts; e) refractory ALL (5-20% blasts in BM) with/without expression of CD66 on blasts; f) refractory AML (> 20% blasts in BM) with expression of CD66 on blasts; g) refractory ALL (> 20% blasts in BM) with expression of CD66 on blasts; 2) be ? 1 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 normal cardiac function without specific treatment; 8) have adequate organ function (as indicated by Table 3, chapter 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). Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study admission: 1) patients with CNS disease; 2) patients with BM cellularity < 10%; 3) patients with refractory disease (? 20% blasts in BM) with no expression of CD66 on blasts; 4) patients with positive human-anti-murine antibodies; 5) patients with compromised organ function (as indicated by Table 3, chapter 5), within 30 days prior to 111In infusion; 6) patients with chronic extensive GvHD; 7) patients with an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment; 8) patients who are pregnant or lactating; 9) patients with any other severe concurrent disease, which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether a radiolabelled antibody that tergets the bone marrow (the anti-CD66) can be administered safely to children as part of the preparative treatment prior to haematopoietic stem cell transplantation. To evaluate the safety (and maximum tolerated dose) and feasibility of targeted radiotherapy delivered by 90-Yttrium-labelled anti-CD66 monoclonal antibody within a reduced intensity conditioning regimen in children with relapsed/refractory leukaemia undergoing allogeneic haematopoietic stem cell transplantation. ;Secondary Objective: 1) to determine the disease response and disease-free survival of children affected by relapsed/refractory leukaemia receiving targeted radiotherapy as part of their conditioning prior to haematopoietic stem cell transplantation; 2) to evaluate the timing of myeloid and platelet engraftment after 90-Yttrium-labelled anti-CD66 monoclonal antibody treatment within a reduced intensity conditioning; 3) to evaluate the quality of donor engraftment after haematopoietic stem cell transplantation. ;Primary end point(s): To evaluate the safety (and maximum tolerated dose) and feasibility of targeted radiotherapy delivered by 90-Yttrium-labelled anti-CD66 monoclonal antibody with reduced intensity conditioning in children with relapsed/refractory leukaemia undergoing allogeneic stem cell transplantation. ;Timepoint(s) of evaluation of this end point: At time of 111-Indium infusion, day -14 (day of 90-Yttrium infusion)pre HCT, day -7 pre HCT, day zero, 7, 14, 21, 30, 60, 90, 180, 360 post HCT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) to determine the disease response and disease-free survival of children affected by relapsed/refractory leukaemia receiving targeted radiotherapy as part of their conditioning prior to haematopoietic stem cell transplantation; 2) to evaluate the timing of myeloid and platelet engraftment after 90-Yttrium-labelled anti-CD66 monoclonal antibody treatment within a reduced intensity conditioning; 3) to evaluate the quality of donor engraftment after haematopoietic stem cell transplantation. 4) to determine the pharmacokinetics/biodistribution of 111-Indium-labelled anti-CD66 monoclonal antibody; ;Timepoint(s) of evaluation of this end point: At time of 111-Indium infusion (and day 1, 2, 4, 5 post infusion of 111-Indium), day -14 (day of 90-Yttrium infusion)pre HCT, day -7 pre HCT, day zero, 7, 14, 21, 30, 60, 90, 180, 360 post HCT. | — |
Countries
United Kingdom
Contacts
Public ContactDr Robert Chiesa
Great ormond Street Hospital
Outcome results
None listed