E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intravenous azacitidine 100 mg/m2, Days 1 to 7 of a 28-day cycle for up to 3 cycles initially.
In case of decline of MRD during azacitidine treatment additional cycles are allowed (maximum 6 cycles).
|
|
E.1.1.1 | Medical condition in easily understood language |
Infusion of azacitidine (study drug) to the patient up to 6 times. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059034 |
E.1.2 | Term | Acute myeloid leukaemia recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 the effect of azacitidine treatment in AML subjects at molecular relapse after CR1 with regard to molecular response prior to further treatment (reinduction / HSCT) |
|
E.2.2 | Secondary objectives of the trial |
To assess safety of azacytidine treatment in children and adolescents with a molecular relapse of AML. Disease free and overall survival post molecular relapse; quality of life (questionnaire, AE reports). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 3 months to <21 years with documented diagnosis of AML according to WHO classification with at least one quantitative genetic maker, e.g. one of the following aberrations:
• t(8;21); RUNX1/RUNX1T1 • inv(16); CBFb/MYH11 • t(9;11); MLL/AF9 • t(10;11); MLL/AF10 • NPM1 • WT1; etc.
2. Molecular remission (MRD in PB less than 5 x 10-4) confirmed at the start of last consolidation course or within 1 month after completion of consolidation treatment
3. Detection of a confirmed molecular relapse of an AML
4. Understand and voluntarily provide permission (subjects and when applicable, parental/legal representative(s)) to the ICF prior to conducting any study related assessments/procedures
5. Able to adhere to the study visit schedule and other protocol requirements
6. Lansky performance score at least equal to 50; or Karnofsky performance status at least equal to 50, whichever is applicable
7. Negative serum pregnancy tests for females of child bearing potential within 10 days prior to treatment
|
|
E.4 | Principal exclusion criteria |
1. Concomitant treatment with any other anticancer therapy except those specified in protocol
2. HSCT within previous 3 months
3. Treated by any investigational agent in a clinical study within previous 4 weeks
4. Pregnancy or lactating
5. FAB type M3 leukemia (acute promyelocytic leukemia)
6. Therapy-related AML
7. AML of Down syndrome or other congenital syndromes giving rise to leukemia or treatment complications
8. Symptomatic cardiac disorders (CTCAE 4.0 Grade 3 or 4)
9. Evidence of invasive fungal infection or other severe systemic infection requiring treatment doses of systemic/parenteral therapy including known active viral infection with human immunodeficiency virus (HIV) or Hepatitis Type B and C
10. Any other organ dysfunction (CTCAE 4.0 Grade 3 or 4) that will interfere with the administration of the therapy according to this protocol
11. Ongoing severe toxicities (CTCAE 4.0 Grade 3 or 4) of prior chemotherapy/stem cell transplantation
12. Hypersensitivity to the active substance or other excipients contained in the investigational medical product listed in the summary of product characteristics (SmPC) or Investigators Brochure (IB).
13. Abnormal liver function: • serum bilirubin > 3 x ULN • ALT or AST > 5 times ULN
14. Symptomatic CNS-involvement or isolated extramedullary disease at initial diagnosis
15. Female and male subjects with child bearing potential who avoid using highly effective anticonceptive measure(ment)s |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint based on molecular response will be assessed at the end of the azacitidine treatment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Toxicities • Event-free-survival • Disease free survival • Overall-survival • Quality of life
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | Yes |
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 | Yes |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Austria |
Belgium |
Czech Republic |
Denmark |
European Union |
Finland |
France |
Germany |
Italy |
Netherlands |
Norway |
Poland |
Slovakia |
Sweden |
Switzerland |
United Kingdom |
|
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
|
LVLS + 28 days safety follow up |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |