The primary objective is to assess the treatment effect on response rate (MDS: either completeremission [CR], partial remission [PR], or marrow CR; JMML: either clinical completeremission [cCR] or clinical partial remission [cPR]); at Cycle 3 Day 28…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Response Rate at Cycle 3 Day 28
Secondary outcome
- Cytogenetic Response for MDS subjects; Cytogenetic and Molecular Response for
JMML subjects
- Duration of response
- Time to response
- Time to progression
- Leukemia free survival
- Overall survival
- Deoxyribonucleic acid methylation status in BM on Days 1 and 15 of Cycle 1,
Day 28 of Cycle 3, pre-HSCT, and at the time of relapse/progression
- Percentage of subjects undergoing HSCT
- Time to first HSCT
-Safety defined by frequency and severity of treatment emergent AEs
- Pharmacokinetics
Background summary
Based on the available adult and pediatric data, azacitidine seems to be a very
promising
treatment option for pediatric advanced MDS and JMML. In addition to the
clinical response
rates outlined above, cytogenetic and molecular responses have also been
observed with the use
of azacitidine, unlike the responses seen with current therapeutic agents,
which provide more
moderate response with increased toxicity. This further supports the value of
studying
azacitidine given prior to HSCT in MDS/JMML and the potential benefit of giving
azacitidine in
this patient population.
Study objective
The primary objective is to assess the treatment effect on response rate (MDS:
either complete
remission [CR], partial remission [PR], or marrow CR; JMML: either clinical
complete
remission [cCR] or clinical partial remission [cPR]); at Cycle 3 Day 28 and to
compare against
standard therapy using a matched-pairs analysis of historical data.
Study design
This is a prospective, open-label, Phase 2 study consisting of 2 parallel
experimental arms, one
for each disease group: MDS and JMML.
Twenty subjects with MDS and 35 JMML subjects evaluable for the primary
endpoint (ie,
subjects that receive at least 1 dose of investigational product [IP]) will be
enrolled at
approximately 45 centers in Europe. If, during Stage 1 evaluation, less than 2
subjects are
observed with a CR, PR, or marrow CR after 3 cycles of azacitidine in the first
9 subjects with
MDS, then enrollment will be stopped. Similarly, if less than 3 subjects are
observed with a cPR
or cCR after 3 cycles of azacitidine in the first 18 subjects with JMML, then
enrollment will be
stopped.
Intervention
Azacitidine 75 mg/m2, either IV or SC, will be administered QD on Days 1 to 7
of a 28-day
cycle for a minimum of 3 cycles and a maximum of 6 cycles, provided that the
subject does not
have disease progression (based on an independent central review of responses -
see above under
*Study Design*) or HSCT from Cycles 4 through 6.
Study burden and risks
Please refer to the table of evens in the protocol for a complete overview of
the procedures.
Azacitidine 75 mg/m2, either IV or SC, will be administered QD on Days 1 to 7
of a 28-day
cycle for a minimum of 3 cycles and a maximum of 6 cycles, provided that the
subject does not
have disease progression (based on an independent central review of responses -
see above under
*Study Design*) or HSCT from Cycles 4 through 6.
Risks associated with participation in this study are the normal risks of
pediatric oncology treatments.
Possible side effects of Vidaza:
• anemia
• low number white blood cells with or without fever
• decrease in number of platelets
• Infections, including pulmonary infection or urinary tract infection
• nausea
• vomiting
• diarrhea
• pain in the stomach
• constipation
• tired, unwell, or weak fealing
• sore throat
• less appetite
• pain
• dizziness
• shortness of breath with or without exercise
• skin rash
• itching
• bruise
• response to place of injection
Morris Avenue 86
New Jersey 07901
US
Morris Avenue 86
New Jersey 07901
US
Listed location countries
Age
Inclusion criteria
MDS:
1. Patient has newly diagnosed advanced primary or secondary MDS with
immature cells in blood or bone marrow or chromosomal
abnormality linked to secondary MDS. Blood and bone marrow samples
confirming diagnosis within 14 days prior to ICF as for the MDS.
JMML:
1. Patient has newly diagnosed JMML, with samples from blood and bone
marrow confirming diagnosis and specific genetic changes.;Both MDS and JMML:
2.Patient has a Lansky play score/ Karnofsky performance status at
least equal to 60
3.Patient has a normal renal function and a normal liver function.
4.Subjects should be between 1 month to less than 18 years at time of
signing ICF/ IAF
Exclusion criteria
MDS exclusions:
1.Patient has an illness caused by 'germline genetic defects'.
2.Patient has inherited bone marrow failure syndrome.
JMML exclusion:
1.Patient has germline genetic defects.
Both:
1.Patient has organ dysfunction that will interfere with the
administration of the therapy according to this protocol.
2.Hypersensitivity to azacitidine
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 |
|---|---|
| EudraCT | EUCTR2014-002388-13-NL |
| CCMO | NL50476.078.15 |