E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or refractory Acute Myeloid Leukemia (AML) |
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E.1.1.1 | Medical condition in easily understood language |
Recurring or persistent acute blood cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067859 |
E.1.2 | Term | Allogenic stem cell transplantation |
E.1.2 | System Organ Class | 100000004865 |
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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 evaluate whether stem cell transplantation (SCT) from a matched sibling donor (MSD) is equivalent to a matched unrelated donor (MUD) in second complete remission (CR2) (see statistics part). • To evaluate whether “FLAMSA” increases survival as compared to a survival rate estimated from historical data (studies AML-BFM and Relapsed AML 2001/1) in children suffering from refractory AML or relapsed AML responding poorly to reinduction therapy. • To evaluate whether HSCT from haploidentical donors for children having no matched donor increases survival as compared to a survival rate estimated from historical data (studies AML-BFM and Relapsed AML 2001/1) in children suffering from refractory AML or relapsed AML.
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E.2.2 | Secondary objectives of the trial |
• Prospective evaluation of event free survival (EFS), LFS, and OS after SCT from either a MSD or a MUD. • To evaluate whether it is feasible to standardize transplantation procedures in children with AML within the AML-Berlin/Frankfurt/Münster (BFM) study network. • Decrease of transplantation associated mortality by standardized donor selection criteria. • To further evaluate the contribution of immunomediated effects for the treatment of children suffering from very high risk AML. • Prospective evaluation of late toxicities.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged between 0-21 years • Patients suffering from either refractory de novo AML or relapsed AML or patients with high risk AML in CR1 (As defined by AML as secondary malignancy (not MDS-related) or with high-risk cytogenetic aberrations like the following: 12p, monosomy 7, t(4;11), t(5;11), t(6;11), t(6;9), t(7;12), t(9;22), t(8;16), t(10;11), complex karyotype or WT1mut/FLT-ITD). • In sexually active patients two reliable contraception methods are used. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (e.g. diaphragm, cervical cap, or condom) or with a spermicide. • Written informed consent of patient, parents or legal guardians
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E.4 | Principal exclusion criteria |
• Severe renal impairment (GFR < 30% predicted for age) • Pregnant or lactating females • Current participation in another clinical trial • Patients ≥ 12 years old for Group 1 (“BuCyMel”) (patients younger that 12 years continue to be included)
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E.5 End points |
E.5.1 | Primary end point(s) |
Main endpoint of the study is survival measured from date of diagnosis of relapse or nonresponse to death of any cause or last follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Death of any cause or last follow-up (SCT + 5 years of follow-up) |
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E.5.2 | Secondary end point(s) |
1. Survival measured from the date of SCT 2. Acute and chronic GVHD 3. Other acute and late toxicities |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. SCT + 5 years of follow-up 2. SCT + 5 years of follow-up 3. SCT + 5 years of follow-up |
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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 | No |
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) | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |