To determine the safety, clinical efficacy, and effect of azacitidine on the body,within the body and interactions within the body in children and young adults with newly diagnosed advanced Myelodysplastic Syndromes or Juvenile myelomonocyctic leukemia before transplantation of the bone marrow and blood. At the end of the study, the data will be compared to data from an older study of patients with the same diseases.

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2014-002388-13-SE
• Date of registration: 09/03/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: To determine the safety, clinical efficacy, and effect of azacitidine on the body,within the body and interactions within the body in children and young adults with newly diagnosed advanced Myelodysplastic Syndromes or Juvenile myelomonocyctic leukemia before transplantation of the bone marrow and blood. At the end of the study, the data will be compared to data from an older study of patients with the same diseases.
• Scientific title: A Phase 2, multicenter, open-label study to evaluate the pharmacokinetics, pharmacodynamics, safety and activity of azacitidine and to compare azacitidine to historical controls in pediatric subjects with newly diagnosed advanced myelodysplastic syndrome or juvenile myelomonocytic leukemia before hematopoietic stem cell transplantation.
• Date of first enrolment: 06/08/2015
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002388-13
• 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: comparison against a historical control arm using data collected retrospectively from EWOG registry; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
MDS:

1. Patient has newly diagnosed advanced primary or secondary MDS with an amount of immature cells in blood or bone marrow or chromosomal abnormality linked to secondary MDS. Blood or 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 within the 14 days prior to informed consent/informed assent signature, with specific alteration in genes (which carry the information that determines a person characteristics) in the body

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 55
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:
MDS exclusions:

1.Patient has an illness caused by 'genetic defects' (which cause abnormalities in the information that determine a person's characteristics).
2.Patient has inherited disease that cause bone marrow (the soft tissue inside of the bone) failures.

JMML Exclusion:
1.Patient has a specific deviation in so called Germline.

Both:
1.Patient has any other organ dysfunction that will interfere with the administration of the therapy according to this protocol.
2.Hypersensitivity to azacitidine



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

newly diagnosed advanced myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML) prior to hematopoietic stem cell transplantation (HSCT)
MedDRA version: 20.0 Level: LLT Classification code 10054439 Term: Juvenile chronic myelomonocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851
MedDRA version: 20.1 Level: PT Classification code 10023249 Term: Juvenile chronic myelomonocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Vidaza 25 mg/ml powder for suspension for injection
Product Name: Azacitidine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10 (Total 100mg)-

Trade Name: Vidaza 25 mg/ml powder for suspension for injection
Product Name: Azacitidine
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25 (Total 100mg)-

Primary Outcome(s)

Main Objective: The primary objective is to assess the treatment effect on response rate (MDS: CR, PR, or marrow CR; JMML: either cCR or cPR) at Cycle 3 Day 28 and to compare against standard therapy using a matched-pairs analysis with historical data.

Primary end point(s): MDS:
Proportion of subjects with CR, PR or marrow CR according to modified criteria based on Table 3 in Cheson 2006, adapted to pediatric reference values at 3 months (Cycle 3, Day 28). Response must be sustained for at least 4 weeks either in the 4-week period preceding or succeeding Cycle 3 Day 28 (ie, sustained over the period Cycle 2 Day 28 to Cycle 3 Day 28, or Cycle 3 Day 28 to Cycle 4 Day 28).

JMML:
Proportion of subjects with sustained cCR or cPR according to the International JMML response criteria in Niemeyer 2015 at 3 months (Cycle 3, Day 28). Response must be sustained for at least 4 weeks either in the 4-week period preceding or succeeding Cycle 3 Day 28 (ie, sustained over the period Cycle 2 Day 28 to Cycle 3 Day 28, or Cycle 3 Day 28 to Cycle 4 Day 28).

Secondary Objective: The secondary objectives are to further evaluate safety, efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of azacitidine in this subject population.

Timepoint(s) of evaluation of this end point: MDS:
Response will be evaluated on Day 1 of Cycles 2 and 3, Day 28 of Cycle 3, if there is a suspected disease progression after Cycle 3 Day 28, Day 28 of Cycle 6 (if applicable), and pre-HSCT (Hematopoietic Stem Cell Transplantation , transplant of cells)

JMML:
Response will be evaluated on Day 1 of Cycles 2 and 3, Day 28 of Cycle 3, if there is a suspected disease progression after Cycle 3 Day 28, Day 28 of Cycle 6 (if applicable), and pre-HSCT (Hematopoietic Stem Cell Transplantation , transplant of cells)

Secondary Outcome(s)

Secondary end point(s): 1.Cytogenetic Response for MDS subjects
2.Cytogenetic and Molecular Response for JMML subjects
3.Duration of response (DoR)
4. Time to response (TTR)
5.Time to progression (TTP)
6.Leukemia free survival (LFS)
7.Overall survival (OS)
8.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
9.Percentage of subjects undergoing HSCT
10.Time to first HSCT
11.Safety defined by frequency and severity of treatment emergent AEs
12.Pharmacokinetics (PK)

Timepoint(s) of evaluation of this end point: 1,2.C1D1,C2D1,C3D1,D28 if there is suspected disease progression after C3D28,C6D28 (if applicable)&pre-HSCT(only if >21 days since the last BM aspirate)in order to evaluate response to treatment
3.1st observed response until either disease progression/any cause of death
4.1st study dose day until a response.
5.1st study dose day until either disease progression/death due to progression
6,7,9,10.during follow-up period
8.C1D1,C1D15,C3D28, at time of relapse/disease progression&pre-HSCT for extraction of DNA
11.during the course of study
12.C1D5,D6 Prior to dosing,C1D7 prior to dosing,postdose 5mins(IV use azacitidine application) or 15mins postdose(SC use),postdose 30mins, 1hr, 2hrs, 4hrs, 6hrs IV and SC use.

Secondary ID(s)

AZA-JMML-001

2014-002388-13-DE

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date:
Contact: