Azacitidine in children with MDS or JMML

• Register: EUCTR
• Last refreshed on: 4 May 2020
• Main ID: EUCTR2010-022235-10-DK
• Date of registration: 27/06/2013
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC
• Public title: Azacitidine in children with MDS or JMML
• Scientific title: A Phase I/II study of Azacitidine (Vidaza®) in pediatric patients with newly diagnosed or relapsed high-grade pediatric MDS or JMML - Azacitidine in high grade MDS and JMML pediatric patients
• Date of first enrolment: 27/06/2013
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022235-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: historical data when time to transplant was not bridged with chemotherapy Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, Denmark, Germany, Ireland, Italy, Netherlands, Spain

Contacts

• Name: S. Ramnarain
• Affiliation: Trial Office

• Name: S. Ramnarain
• Affiliation: Trial Office

Key inclusion & exclusion criteria

Inclusion criteria:
In this study 4 subgroups of patients are eligible, which will be enrolled in 4 different strata:

•stratum 1: newly diagnosed patients with advanced MDS (RAEB or RAEB-t) in a ‘pre stem cell transplantation window’.
•stratum 2: relapsed patients with advanced MDS in a ‘re-transplantation window’. At relapse azacitidine may also be continued when a 2nd transplant is not feasible, as long as the patient benefits from treatment.
•stratum 3: newly diagnosed patients with JMML in a ‘pre-stem cell transplantation window’.
•stratum 4: relapsed patients with JMML in a ‘re-transplantation window’. Azacitidine may also be continued when a 2nd transplant is not feasible and as long as the patient benefits from treatment.
•straum 5:newly diagnosed or relapsed patients with secondary advanced MDS, occurring after
chemotherapy, radiotherapy and or stem-cell transplantation, or secondary cases after
prior treatment for aplastic anemia. Note: secondary MDS cases after bone-marrow failures or familial cases are not eligible


General conditions:
•Advanced primary or secondary MDS or JMML confirmed by the diagnostic criteria as specified in the EWOG-MDS 2006 protocol (see appendix 1)
•1 month to = 18 years old
•Lansky play score = 60; or Karnofsky performance status = 60 (appendix 2)
•Life expectancy = 3 months
•Normal renal function defined as less than or equal to NCI-CTCAE grade 1 (max 1.5 x ULN).
•Normal liver function defined as less than or equal to NCI-CTCAE grade 1 (max 2.5 x ULN for transaminases and bilirubin)
•No chemotherapy within 3 weeks of start of study medication. For 6-MP or low-dose cytarabine in JMML patients 1 week wash-out time is sufficient.
•For JMML patients: saturation >92% without additional supply of oxygen
•For JMML patients: peripheral blood monocyte count > 1.0x109/l
•For relapsed patients following HSCT: recovery of all acute toxic effects of prior chemotherapy/stem-cell transplantation.
•Able to comply with scheduled follow-up and with management of toxicity.
•For patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study. If applicable, use of an effective contraceptive method.
•Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
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:
Prior or current history:
•Other serious illnesses or medical conditions
•Genetic abnormalities indicative of AML
•JMML patients in whom a diagnosis of Noonan syndrome is suspected based on clinical history and/or presenting symptoms
•Patients with secondary MDS with underlying bone-marrow failure syndromes or with familial MDS
•Isolated extramedullary disease
•Symptomatic CNS-involvement
•Current uncontrolled infection
•Cardiac toxicity (shortening fraction below 28%)
•Concurrent treatment with any other anti-cancer therapy is not allowed
•Pregnant or lactating patients
•Patients who cannot be regularly followed up for psychological, social, familial or geographic reasons
•Patient with expected non compliance to toxicity management guidelines
•Prior treatment with a demethylating agent
•Allergy to azicitidine or mannitol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic Leukemia (JMML)
MedDRA version: 14.1 Level: LLT Classification code 10054439 Term: Juvenile chronic myelomonocytic leukemia System Organ Class: 100000004864
MedDRA version: 14.1 Level: LLT Classification code 10068361 Term: MDS System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: vidaza
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: AZACITIDINE
CAS Number: 320672
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: -To determine the safety and tolerability of azacitidine in newly diagnosed and relapsed advanced MDS and JMML
-To determine (preliminary) the hematological remission rate in these patients
-To describe the durability of response and long-term follow-up, including that of patients undergoing stem-cell transplant after treatment with azacitidine
-To determine the plasma pharmacokinetic parameters of azacitidine
-To study the pharmacodynamic effects of azacitidine in pediatric advanced MDS or JMML

Primary end point(s): The primary objective of this study is to establish a recommended dose and preliminary efficacy of azacitidine in children with newly diagnosed or relapsed advanced MDS or JMML.

Timepoint(s) of evaluation of this end point: Primary endpoint may be limited by Dose Limiting toxicities in cycle 1 but otherwise full evaluation of the primary endpoint is possible after of treatment and after end of study.

Main Objective: To establish the recommended dose and preliminary efficacy of azacitidine in children with newly diagnosed and relapsed advanced MDS or JMML.

Secondary Outcome(s)

Secondary end point(s): Other objectives concern:
•To determine the safety and tolerability of azacitidine in newly diagnosed and relapsed MDS and/or JMML.
•To determine (preliminary) the hematological remission rate in these patients.
•To describe the durability of response and long-term follow-up (at least 1 year after end of treatment), including that of patients undergoing stem-cell transplant after treatment with azacitidine.
•To determine the plasma pharmacokinetic parameters of azacitidine.
•To study the pharmacodynamic effects of azacitidine in pediatric MDS or JMML.

Timepoint(s) of evaluation of this end point: For most endpoints after 3 cycles, and others after 1 year after HSCT or 1 year after last treatment with azacitidine when no HSCT is given

Secondary ID(s)

Nederlands Trial Register

ITCC-015/EWOG-MDS-Azacytidine-2010

2010-022235-10-NL

Source(s) of Monetary Support

Celgene

Go4Children Foundation

Ethics review

Status: Approved
Approval date: 23/05/2013
Contact: