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A Study of Safety, Efficacy and Pharmacodynamics of Azacitidine in Children and Young Adults With Acute Myeloid Leukemia.

NCT02450877 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 7

Last updated 2019-12-20

No results posted yet for this study

Summary

This study is a randomized, multicenter, open-label, Phase 2 study that will be run in 2 parts: a safety run-in part to determine the dose of azacitidine and then a second part to determine the efficacy of that dose in children and young adults with acute myeloid leukemia in molecular relapse after their first complete remission.

Indication Treatment of children and young adults with molecular relapse of acute myeloid leukemia (AML) after first complete remission (CR1).

Objectives Primary Objectives 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) post randomization.

Secondary Objectives 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.

Study Design The population of this trial consists of children and young adults with AML who achieved a complete response (CR) with molecular remission, defined as Minimal Residual Disease (MRD) less than 5 x 10-4, following their initial induction therapy and who subsequently have a molecular relapse (defined as increase in MRD level by at least 1 log \[10-fold\] to a level greater than or equal to 5 x 10-4 despite a normal percentage \[\<5%\] of myeloblasts in the bone marrow \[BM\] aspirate and peripheral blood \[PB\], and in the absence of proven histological extramedullary relapse). Eligible subjects have a documented diagnosis of AML with at least one of the following molecular aberrations t(8;21), RUNX1-RUNX1T1, inv(16), CBFb/MYH11, t(9;11), MLL-AF9, NPM1 mutation, or FLT3-ITD mutation. Enrolled/randomized pediatric subjects will be followed with regular MRD testing in order to detect a molecular relapse.

In the safety run-in part, up to 12 subjects aged 3 months to less than 18 years will be enrolled. Six subjects will be enrolled in the first cohort of 100 mg/m2 azacitidine administered intravenously (IV) on Days 1 to 7 of a 28-day cycle. Six additional subjects could be enrolled into a second cohort of 75 mg/m2 azacitidine administered IV on Days 1 to 7 of a 28-day cycle depending on the safety and tolerability results of the 100 mg/m2 cohort.

In the randomized part of the study at least 68 subjects will be randomized (or more depending on whether at least 64 subjects are evaluable for the primary endpoint), with at least 60 of the subjects being less than 18 years of age.

Both parts of the study, the safety run-in part and the randomized part, will contain 3 periods: the screening period, the treatment period and the follow-up period. The screening period will last no more than 10 days in the safety run-in part after which the subjects may be enrolled and treated. In the randomized part, the screening period will last an indefinite amount of time until detection of a molecular relapse in the PB followed by confirmation of the relapse in both PB and BM aspirate, at which point the subject may then be randomized. Subjects will be treated with azacitidine (safety run-in part) or in accordance to their assigned treatment arm (randomized part). Upon discontinuation from the treatment period, subjects will enter into the follow-up period which will last up to 2 years from last patient enrolled/randomized.

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DRUG

Azacitidine

OTHER

Control Arm

Sponsors & Collaborators

  • Celgene

    lead INDUSTRY

Principal Investigators

  • Bouchra Benettaib, MD · Celgene Corporation

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
3 Months
Max Age
21 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-08-12
Primary Completion
2018-10-10
Completion
2019-10-08

Countries

  • Denmark
  • Germany
  • Netherlands

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02450877 on ClinicalTrials.gov