• Primary 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 Objectives:o To assess safety of…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint based on molecular response will be assessed at the end of
the azacitidine treatment.
Secondary outcome
• Toxicities
• Event-free-survival
• Disease free survival
• Overall-survival
• Quality of life
Background summary
The majority of patients with newly diagnosed AML achieve a CR after induction
chemotherapy. However, relapse occurs in about one-third of children and far
fewer achieve CR after reinduction chemotherapy. The probability of survival at
4 years is 38% in the most recent study of relapsed AML patients (Kaspers,
2013), which is consistent with earlier studies showing survival rates around
30%. Failure to achieve CR after reinduction is associated with failure of
subsequent attempts at curative therapy such as HSCT. Further improvements of
current treatment, including improvements in remission induction for relapsed
patients are thus required.
Study objective
• Primary 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 Objectives:
o To assess safety of azacitidine treatment in children and adolescents with a
molecular relapse of AML
o Disease free and overall survival post molecular relapse
o Quality of life (questionnaire, AE reports).
Study design
Prospective, multi-center, open label, phase 2 trial
Intervention
Intravenous azacitidine 75 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).
Study burden and risks
Possible adverse events of this study are:
• anemia,
• low number of white blood cells with or without fever
• infections, inlcuding pulmonary infection or urinary tract infection
• nausea
• vomiting
• diarhea
• pain in the stomach
• constipation
• tired, unwel or feeling weak
• sore throat
• less appetite
• pain
• dizziness
• shortness of breath with or whithout exercise
• skin rash
• itching
• bruising
• response to place of injection
Hufelandstrasse 17
Essen 45147
DE
Hufelandstrasse 17
Essen 45147
DE
Listed location countries
Age
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
• FLT3-ITD
• WT1; etc.
2. First complete 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
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:
a. serum bilirubin > 3 x ULN or
b. 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | DRKS00015449 |
| EudraCT | EUCTR2017-003422-32-NL |
| CCMO | NL66579.078.18 |