This study has been transitioned to CTIS with ID 2023-508129-28-00 check the CTIS register for the current data. The primary objective of this study is to characterize the pharmacokinetic (PK) profile of asciminib in pediatric patients, with the…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to characterize the pharmacokinetic (PK)
profile of asciminib in pediatric patients, with the goal of identifying the
pediatric formulation dose (fed) leading to asciminib exposure comparable to 40
mg BID in adult patients (fasted).
Secondary outcome
The secondary objectives of this study are:
* To assess the safety and tolerability of asciminib.
* To assess pharmacodynamic markers of asciminib*s anti-leukemic activity.
* To assess acceptability and palatability of the pediatric formulation.
* To assess long-term safety of asciminib.
Background summary
CML is a form of cancer of the bonemarrow and has 3 phases, the chronic fase is
the first fase. In this fase, in this fase there are often few noticable
effects. Without sufficient treatment the chronic fase can proceed into the
second and third fases.
The form of CML treated in this study is Philadelphia chromosoom-positive. This
means that there is an aberrant chromosome in the bonemarrow. This chromosome
contains a fusion gene: the BCR-ABL gene. This gene produces a protein that
causes CML, the BCR-ABL protein.
Asciminib is a tyrosinekinaseinhibitor (TKI), which is a form of targeted
therapy. These types of drugs inhibit the BCR-ABL protein, and thereby kills
CML-cells. TKIs work for the majority of patients with CML, however it is
possible for resistance to a current treatment with TKIs to form. In which case
the effectiveness of treatment might diminish or even stop. This is because the
BCR-ABL gene can mutate and no longer be susceptable to a particular TKI. At
that time it might be necessary to switch to a different TKI.
Asciminib has not yet been approved by the Dutch health authority, but has been
approved for treatment of adults with CML by the FDA. Prior to this the effects
of asciminib have been studied in various forms of leukemia in different fases
of the disease in 530 adults. For younger childeren an additional formulation
consisting of 1mg mini-tablets has been developed. The mini-tablets are kept in
a capsule to allow for more precise dosing, capsules varying from 5 to 50 mg of
asciminib are available and dosing will be determined based on body weight.
Study objective
This study has been transitioned to CTIS with ID 2023-508129-28-00 check the CTIS register for the current data.
The primary objective of this study is to characterize the pharmacokinetic (PK)
profile of asciminib in pediatric patients, with the goal of identifying the
pediatric formulation dose (fed) leading to asciminib exposure comparable to 40
mg BID in adult patients (fasted).
Study design
This is a multi-center, open-label, single arm study to determine the
appropriate dose of asciminib (pediatric formulation) in pediatric patients
aged 1 to < 18 years old with Ph+ CML-CP, who are resistant or intolerant to at
least one prior TKI.
There will be two study treatment groups:
* The pediatric formulation group, consisting of Part 1, Part 2 and part 3, in
which the participants receive a body weight adjusted dose of pediatric
mini-tablets with food, Part 1 and 2 will have BID dosing, part 3 will explore
QD dosing.
* The exploratory adult formulation group, in which the participants receive a
flat dose of asciminib 40 mg BID of the adult tablet in the fasted state.
Intervention
Asciminib in 40mg tablet formulation, or mini-tablets in capsule form.
Study burden and risks
Participation in this study exposes the participant to risks associated with
using asciminib (the possible side effects) and the possible side-effects of
the study assessments. See above sections for more details, or protocol section
8.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
* Male or female participants:
a. Pediatric formulation group: >= 1 and less than 18 years of age at study
entry.
b. Adult formulation group: >= 14 and less than 18 years of age and body weight
of >= 40 kg at study entry.
* Participants with Ph+ CML-CP must meet all of the following laboratory values
at the screening visit. In the case where bone marrow blast and promyelocyte
counts are available, these will be accepted if done within 56 days prior to
the screening visit, to avoid unnecessary repetition of this test.
a. 15% blasts in peripheral blood and bone marrow
b. < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow
c. < 20% basophils in the peripheral blood
d. Neutrophils >= 1.5 x 10^9/L (or white blood cell (WBC) >= 3 x 10^9/L if
neutrophils are not available) and platelet count >= 100 x 10^9/L
e. No evidence of extramedullary leukemic involvement, with the exception of
hepatosplenomegaly
* Prior treatment with a minimum of one TKI.
* Failure or intolerance to the most recent TKI therapy at the time of
screening.
* Evidence of typical BCR-ABL fusion gene (BCR-ABL1) transcript [e14a2 and/or
e13a2] at the time of screening which are amenable to standardized real time
quantitative polymerase chain reaction (RQPCR) quantification.
Exclusion criteria
* Known presence of the T315I mutation prior to study entry.
* Known second chronic phase of CML after previous progression to AP/BC.
* Previous treatment with a hematopoietic stem-cell transplantation.
* Patient planning to undergo allogeneic hematopoietic stem cell
transplantation.
* Cardiac or cardiac repolarization abnormality.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508129-28-00 |
| EudraCT | EUCTR2021-001286-20-NL |
| ClinicalTrials.gov | NCT04925479 |
| CCMO | NL79020.041.22 |