A Study of Safety, Efficacy and Pharmacodynamics of Azacitidine in Children and Young Adults With Acute Myeloid Leukemia.
Status:
Completed
Trial end date:
2019-10-08
Target enrollment:
Participant gender:
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.