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Study to treat the molecular relapsed of AML patients in childhood with Azacitidine

Phase 1
Conditions
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).
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2017-003422-32-DE
Lead Sponsor
Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) gGmbH
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
20
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 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 azacitidine

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 to use secure anti-conceptive measurements

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: 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);Secondary Objective: 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).;Primary end point(s): The primary endpoint based on molecular response will be assessed at the end of the azacitidine treatment.;Timepoint(s) of evaluation of this end point: after max. 196 Days
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): • Toxicities <br>• Event-free-survival<br>• Disease free survival<br>• Overall-survival<br>• Quality of life<br>;Timepoint(s) of evaluation of this end point: after max. 196 Days
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