E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk relapsed or refractory leukaemia in childhood |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | 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. |
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E.5.2 | 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;
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will terminate after the last patient has completed the one-year post-transplant follow up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |