This study has been transitioned to CTIS with ID 2023-504999-25-00 check the CTIS register for the current data. To investigate wether the treatment of children and adolescents with AML can be improvedby means of:1) improved risk-group adapted…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overarching Primary Objective:
• To improve the overall EFS for children and adolescents with newly diagnosed
AML, compared to NOPHO-DBH AML-2012.
* Endpoint: EFS
Primary objective Randomisation Consolidation:
• To demonstrate non-inferiority in disease-free survival of two courses of
consolidation therapy, by omitting HA3E, as compared to three courses, in the
entire standard-risk group eligible for this randomization
* Endpoint: DFS
Secondary outcome
Entire study population:
To improve short-term efficacy by different endpoints, overall survival (OS),
disease-free survival (DFS) and the cumulative incidence of relapse (CIR).
Endpoints:
• Bone marrow blast counts by morphology and multi-color flow cytometry (MFCM)
after course #1 and #2 and before allo-SCT; ORR (CR, CRp, and CRi) and
morphologic leukemia-free state (MLFS) rates after course #1 and #2; MRD
negativity after course #1 and #2 and before allo-SCT; absolute MRD levels
after course #1 and #2 and before allo-SCT.
• OS
• DFS,
• CIR.
Entire study population:
To decrease treatment-related toxicity.
Endpoints:
• Cumulative toxicity, defined as the total of all grades AEs over time, which
are graded by NCI CTCAE version 5.0.
• Non-relapse mortality (NRM).
Randomisation Consolidation:
To improve safety of consolidation treatment.
Endpoints:
• Cumulative toxicity, defined as the total of all grade >=3 AESIs over time,
which are graded by NCI CTCAE version 5.0.
• Non-relapse mortality (NRM).
Background summary
The treatment of children with AML comprises intensive chemotherapy, and
sometimes also stem cell transplantation. To determine the exact treatment,
patients are divided in several risk groups. These are based on characteristics
of AML-cells at diagnosis, and the treatment response at the start of treatment.
The protocol that was used until now for treatment of children and adolescents
with AML showed good results: 70-80% of children survives AML with this
treatment.
When treatment response is poor, or in case of relapse, the prognosis is worse.
It is therefore important to prevent bad response or relapse.
In this new study, the treatment will overall be similar to the previous
protocol. By using data from previous research it is now possible to better
look at characteristics that determine the risk groups for treatment. In
addition, extra treatment options for specific groups were added to the
standard treatment. The overall aim is to improve the treatment of children and
adolescents with AML.
Study objective
This study has been transitioned to CTIS with ID 2023-504999-25-00 check the CTIS register for the current data.
To investigate wether the treatment of children and adolescents with AML can be
improved
by means of:
1) improved risk-group adapted treatment
2) reduced treatment toxicity through shortened consolidation therapy.
Study design
This is a master protocol comprising a complex clinical trial with a
stratification approach to allocate patients to randomized studies described in
the master protocol or linked trials
Intervention
The aim of the randomisation study is to investigate whether treatment with 2
consolidation courses is as effective as treatment with 3 consolidation
courses.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness (if applicable):
The treatment according to this protocol is considered the standard treatment
for children and adolescents with AML.
In the randomisation study is being investigated whether treatment with 2
consolidation courses of children and adolescents with standard risk AML, is as
good as treatment with 3 consolidation courses.
The additional burden compared to standard treatment consists of completing
some questionnaires. Parents / patients will be asked 4 times in total during
the study to complete questionnaires related to Quality of Life. This takes
approximately 10 minutes each time.
The most important risks are standard for pediatric oncology treatment. A risk
related to participation in the consolidation randomization is that by leaving
out on consolidation course, the treatment will be less effective. However,
based on previous research this is not expected, and additionally it is
expected that adverse events will be decreased. The latter is a significant
advantage, since there is even the risk of dying because of the last course of
chemotherapy.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
1) Newly diagnosed AML as defined by the diagnostic criteria in the study
protocol. Note that different blast thresholds may apply for different genetic
abnormalities in case of low blast percentages. The origin of AML must be de
novo (not secondary to bone marrow failure or therapy-related).
2) Age >=1 day and <= 18 years old at initial diagnosis.
3) Written informed consent/assent from patients and/or from parents
or legal guardians for minor patients, according to local law and
regulations. Informed consent should ideally be obtained before day 7 of
induction course 1, as patients that are eligible for the linked quizartinib
trial should be enrolled before the end of induction course 1, and in view of
the planned Mylotarg® randomisation. Thus, standard of care induction treatment
may be started before informed consent has been obtained.
4) Able to comply with scheduled follow-up and with management of
toxicity.
Additional inclusion criteria for the Rc randomization
1) Patients included in the CHIP-AML22 protocol and stratified to Standard Risk
Group according to the stratification algorithm of the protocol
2) Informed consent for participation in randomization Rc
Exclusion criteria
1) Previous chemotherapy or radiotherapy. This includes patients with
therapy-related AML after previous cancer therapy. These patients may be
treated according to the master protocol but will not be part of the formal
study population, and data of these patients will not be collected.
2) Patients with a (known) germline predisposition for bone marrow failure,
like Fanconi anemia. 3) Myeloid Leukemia of Down syndrome (ML-DS). Patients
with ML-DS are recommended to be treated according to the international ML-DS
protocol. Patients with AML and DS older than 5 years who often lack GATA1
mutation and do not have typical myeloid leukemia of DS may be treated
according to the master protocol but will not be part of the formal study
population, hence data of these patients will not be collected.
4) Acute promyelocytic leukemia (APL).
5) Myelodysplastic syndrome (MDS).
6) Juvenile Myelomonocytic Leukemia (JMML).
7) Known intolerance to any of the chemotherapeutic drugs in the protocol.
8) Evidence of cardiac dysfunction (shortening fraction below 28%).
9) Pregnant or lactating patients, or sexually active female patients of
childbearing potential not willing to use an highly effective method of
contraception for the duration of study therapy and up to 7 months after the
completion of all study therapy.
10) Sexually active, fertile male patients, not willing to use an effective
method of contraception, for the duration of study therapy, and up to 6 months
after the completion of all study therapy.
11) Concomitant administration of any other experimental drug under
investigation, or concurrent treatment with any other anti-cancer therapy other
than specified in this protocol or in one of the linked trials linked to this
Master protocol is not allowed.
12) Patients who in the opinion of the investigator, may not be able to comply
with the study requirements of the study.
13) Patients with known active hepatitis B, hepatitis C, or HIV infection.
14) Patients for whom informed consent was not obtained.
Additional information on contraception measures
Females:
A female participant is considered of childbearing potential i.e., fertile,
following menarche and until becoming post-menopausal unless permanently
sterile. Permanent sterilization methods include hysterectomy, bilateral
salpingectomy, and bilateral oophorectomy. As contraception, we suggest the use
of one of the highly effective methods of contraception, as described below.
Highly effective methods of contraception according to the CTFG-2020 guidelines
are those that, alone or in combination, result in a failure rate of less than
1% per year when used consistently and correctly (i.e., perfect use).
Contraception is indicated at least 4 months after last dose of mitoxantrone,
at least 6 months after last dose of cytarabine, etoposide, fludarabine or
methotrexate, and at least 7 months after last dose of quizartinib, whichever
is longer.
Males:
A male patient is considered fertile after puberty unless permanently sterile
by bilateral orchidectomy. If the male is sexually active, he must use a condom
during intercourse, and agree not to father a child or donate sperm during
therapy. Contraception recommendations should also be considered for a
non-pregnant female partner of childbearing potential (see above).
Contraception is indicated at least 6 months after last dose of mitoxantrone,
cytarabine, etoposide, daunorubicin, fludarabine, and at least 4 months after
last dose of quizartinib, whichever is longer.
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
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504999-25-00 |
| EudraCT | EUCTR2022-002885-34-NL |
| CCMO | NL82495.041.22 |