Two parts study, the first part is to determine the dose of azacitidine and the second part is to evaluate the effect of azacitidine compared to no treatment, in children and young adults following a molecular relapse of acute myeloid leukemia after the first complete remission.

A randomized, multicenter, open-label, Phase 2 study with a safety run-in part to evaluate safety, pharmacodynamics and efficacy of azacitidine compared to no anticancer treatment in children and young adults with acute myeloid leukemia in molecular relapse after first complete remission.

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-002172-92-DE

Enrollment

Registered

2014-10-06

Start date

2015-04-27

Completion date

Unknown

Last updated

2020-03-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Treatment of children and young adults with molecular relapse of acute myeloid leukemia (AML) after first complete remission (CR1). MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864

Interventions

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 Co

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: •Patients= 3months and less than 21 years old, who (subject and when applicable parental/ legal representative(s)) must understand and voluntarily sign an Informed Consent or Informed Assent Form. Note: for the Safety Run-in, Patients= 3months and less than 18 years old at the time of informed consent/assent •At the time of signing the ICF/IAF, patients must have documented diagnosis of Acute Myeloid Leukemia and documentation of molecular remission confirmed at the start of last consolidation course or within 1 month after completion of consolidation treatment. •Safety Run-In (At the time of signing ICF/IAF): Detection of molecular relapse within 7 days prior to signing consent/assent and confirmation of molecular relapse during the screening period. Randomized Part (At the time of pre-drug verification visit); Detection of molecular relapse within 7 days prior to signing consent/assent and confirmation of molecular relapse during the screening period. Are the trial subjects under 18? yes Number of subjects for this age range: 80 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

Exclusion criteria: •Concomitant treatment with any other anticancer therapy except those specific in protocol and no maintenance therapy after end of consolidation therapy and confirmed remission. •Hematopoietic Stem Cell Transplantation within previous 3 months •Pregnant or breastfeeding females •Patients with a current disease that can interfere with protocol procedures or study treatment •Hypersensitivity to azacitidine •Symptomatic CNS-involvement or isolated extramedullary disease at initial diagnosis. •FAB type M3 leukemia (acute promyelocytic leukemia) •Therapy-related AML •AML of Down syndrome or other congenital syndromes giving rise to leukemia or treatment complications. •Symptomatic cardiac disorders (CTCAE Grade 3 or 4).

Design outcomes

Primary

Measure	Time frame
Main Objective: Safety Run-in Part -To establish a safe and tolerable dose of azacitidine to be used in the randomized part of the study. Randomized Part -To evaluate the effect of azacitidine treatment in AML subjects at molecular relapse after CR1 when compared to no treatment with regard to the progression-free rate (PFR) at Day 84 (±4 days) postrandomization.;Secondary Objective: Safety Run-in Part -To establish azacitidine plasma pharmacokinetic (PK) parameters in subjects with molecular relapse AML after CR1 and to assess efficacy. Randomized Part -To evaluate the safety, pharmacodynamics (PD), and efficacy of azacitidine treatment in subjects with molecular relapse AML after CR1.;Primary end point(s): Safety Run-in Part : -Identification of a safe and tolerable dose for the randomized part of the study ? -Assessment of treatment-related dose-limiting toxicities (DLTs) ? -Frequency and severity of treatment-related AEs Randomized Part : -Progression-free rate at Day 84 (±4 days) post randomization: Proportion of subjects free from clinical progression (clinical relapse and death from any cause) and from molecular progression (defined as lack of stabilization or lack of decrease in molecular aberrations concerning FLT3-ITD mutated, CBF leukemias (eg, t(8;21) and/or inv(16)), MLL-gene rearrangements or NPM1-mutations using central assessment of BM samples by the central laboratories identified for the study, obtained at time points identically prespecified in both randomization arms) at Day 84 (±4 days) post randomization.;Timepoint(s) of evaluation of this end point: Safety Run-in: The rate of the following treatment-related DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs) version 4.0, occurring during Cycle 1 only will be considered in determining the tolerability of the 100 mg/m2 dose of azacitidine. Once 6 subjects have completed their first cycle of treatment (if not having stopped earlier due to a DLT), sa	—

Measure

Time frame

Main Objective: Safety Run-in Part -To establish a safe and tolerable dose of azacitidine to be used in the randomized part of the study. Randomized Part -To evaluate the effect of azacitidine treatment in AML subjects at molecular relapse after CR1 when compared to no treatment with regard to the progression-free rate (PFR) at Day 84 (±4 days) postrandomization.;Secondary Objective: Safety Run-in Part -To establish azacitidine plasma pharmacokinetic (PK) parameters in subjects with molecular relapse AML after CR1 and to assess efficacy. Randomized Part -To evaluate the safety, pharmacodynamics (PD), and efficacy of azacitidine treatment in subjects with molecular relapse AML after CR1.;Primary end point(s): Safety Run-in Part : -Identification of a safe and tolerable dose for the randomized part of the study ? -Assessment of treatment-related dose-limiting toxicities (DLTs) ? -Frequency and severity of treatment-related AEs Randomized Part : -Progression-free rate at Day 84 (±4 days) post randomization: Proportion of subjects free from clinical progression (clinical relapse and death from any cause) and from molecular progression (defined as lack of stabilization or lack of decrease in molecular aberrations concerning FLT3-ITD mutated, CBF leukemias (eg, t(8;21) and/or inv(16)), MLL-gene rearrangements or NPM1-mutations using central assessment of BM samples by the central laboratories identified for the study, obtained at time points identically prespecified in both randomization arms) at Day 84 (±4 days) post randomization.;Timepoint(s) of evaluation of this end point: Safety Run-in: The rate of the following treatment-related DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs) version 4.0, occurring during Cycle 1 only will be considered in determining the tolerability of the 100 mg/m2 dose of azacitidine. Once 6 subjects have completed their first cycle of treatment (if not having stopped earlier due to a DLT), sa

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Secondary

Measure	Time frame
Secondary end point(s): Safety Run-Part : -Molecular response at Day 84 (±4 days) post Cycle 1 Day 1 (or end of Cycle 3, if not the same date) - Azacitidine plasma PK parameters - Leukemia-free survival (LFS) - Minimal residual disease pre-HSCT - Overall survival Randomized Part: - Changes in DNA methylation (assessments of BM samples using Nano-HELP assay) - Leukemia-free survival - Proportion treated with HSCT - MRD pre-, and 3 and 6 months post-HSCT - Overall survival - Molecular response - Treatment-related mortality/morbidity - Toxicity data after HSCT - Safety;Timepoint(s) of evaluation of this end point: Safety run-in part: -Cycle 1 -Screening, C1D15, C2D1,C3D1, D84 (±4 days) post randomization, and pre-, and 3 and 6 months post-HSCT -at F/U period for up to 2 years from enrollment of last subject -Screening, C2D1 and C3D1, D84 (±4 days) post randomization, and pre-, and 3 and 6 months post-HSCT. If the treatment is discontinued prior 3 cycles, MRD analysis will continue every 28 days until clinical relapse. -during the F/U period for up to 2 years from enrollment of the last subject . Randomized Part: Evaluation of each end point is done as for safety run in phase see (1-5) and incl: -MRD analysis; screening period every 28 days from ICF/IAF, at the Predrug Verification Visit, C2D1 and C2D1, at D84 (±4 days) post randomization, and finally pre-, and 3 and 6 months post-HSCT	—

Measure

Time frame

Secondary end point(s): Safety Run-Part : -Molecular response at Day 84 (±4 days) post Cycle 1 Day 1 (or end of Cycle 3, if not the same date) - Azacitidine plasma PK parameters - Leukemia-free survival (LFS) - Minimal residual disease pre-HSCT - Overall survival Randomized Part: - Changes in DNA methylation (assessments of BM samples using Nano-HELP assay) - Leukemia-free survival - Proportion treated with HSCT - MRD pre-, and 3 and 6 months post-HSCT - Overall survival - Molecular response - Treatment-related mortality/morbidity - Toxicity data after HSCT - Safety;Timepoint(s) of evaluation of this end point: Safety run-in part: -Cycle 1 -Screening, C1D15, C2D1,C3D1, D84 (±4 days) post randomization, and pre-, and 3 and 6 months post-HSCT -at F/U period for up to 2 years from enrollment of last subject -Screening, C2D1 and C3D1, D84 (±4 days) post randomization, and pre-, and 3 and 6 months post-HSCT. If the treatment is discontinued prior 3 cycles, MRD analysis will continue every 28 days until clinical relapse. -during the F/U period for up to 2 years from enrollment of the last subject . Randomized Part: Evaluation of each end point is done as for safety run in phase see (1-5) and incl: -MRD analysis; screening period every 28 days from ICF/IAF, at the Predrug Verification Visit, C2D1 and C2D1, at D84 (±4 days) post randomization, and finally pre-, and 3 and 6 months post-HSCT

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Countries

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

Contacts

Public ContactClinicalTrialDisclosure

Celgene Corporation

ClinicalTrialDisclosure@celgene.com+1-888-260-1599

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026