The main objective of this treatment protocol is to study the efficacy on the treatment response after adding a single gift of Mylotarg. Furthermore, monitoring of toxicity and long term efficacy is also important.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Bone marrow blasts on *day 28* (before the start of the second reinduction
course) given as * 20% or >20%.
Secondary outcome
1. overall survival
2. event-free survival
3. Percentage of patients that achieve CR after two courses of reinduction
chemotherapy
4. Incidence of treatment related mortality and toxicity according to NCI-CTC
criteria
Background summary
Pediatric relapsed AML still has a poor prognosis. The probability of survival
at 4 years is 36% in the most recent study Relapsed AML 2001/01, which is
better than reported before, but not good enough. Further improvements of
current treatment are thus required. Gemtuzumab ozogamicin (GO, Mylotarg®)
consists of a calicheamicin conjugated to the monoclonal CD33 antibody and has
proven to be effective in terms of CR achievement and better overall survival
in adult AML studies and in pediatric AML relapse and salvage therapy studies
with moderate toxicity. The best arm of the current study, which is the
reinduction course including liposomal daunorubicin (DaunoXome®), fludarabine,
cytarabine and G-CSF (DX-FLA) will constitute the standard first reinduction
course of chemotherapy. This regimen will be compared with DX-FLA plus GO at
4.5 mg/m2 as single dose in combination chemotherapy. In case of too much
toxicity with GO at 4.5 mg/m2, the dose will be reduced permanently to 3.0
mg/m2. Patients who do respond poorly to this first course of chemotherapy with
>20% BM blasts on before the start of the second course become eligible for
phase I/II studies. All other patients proceed to the second reinduction
course.
Study objective
The main objective of this treatment protocol is to study the efficacy on the
treatment response after adding a single gift of Mylotarg. Furthermore,
monitoring of toxicity and long term efficacy is also important.
Study design
Intergroup, international, multicenter open label comparative and randomised
phase III study on the efficacy of Mylotarg added to standard reinduction
chemotherapy in children and adolescents with refractory and relapsed AML.
Intervention
All patients eligible for this study will be randomised in a 1:1 fashion for
the addition or not of GO (Mylotarg®) at 4.5 mg/m2 to DX-FLA in the first
course of reinduction chemotherapy. If GO at 4.5 mg/m2 proves to be too toxic,
the dose will be reduced permanently to 3.0 mg/m2. Patients who do respond
poorly to this first course of chemotherapy with >20% BM blasts on *day
28* (before the start of the second course) become eligible for phase I/II
studies. All other patients proceed to the second reinduction course. Patients
who do not achieve a CR after these two courses become eligible for phase I/II
studies. In CR, all patients are eligible for allo-SCT. If more time is needed
to perform that SCT, guidelines for intensive and low-intensity consolidation
are provided in the protocol. The choice for either the intensive or
non-intensive regimen must be based on the anticipated time until SCT and on
the condition of the patient.
Study burden and risks
To get cured, children with relapse AML must be treated. The extent of burden
and risks associated with this treatment are not different than other
treatments used untill now in the Netherlands. This treatment protocol has
strict stopping rules and safety guidelines.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
1. Children and adolescents <18 years of age at start of initial chemotherapy and <21 years of age at start of this relapsed AML treatment
2. Patients with first relapsed or primary refractory AML
3. Patients with a second or subsequent relapsed AML that were not previously treated according to this particular protocol
4. Signed written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations
5. In women of childbearing potential pregnancy must be excluded.
6. Sexually active patients must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized.
Exclusion criteria
1. FAB type M3 (please refer to your local group for the appropriate treatment protocol)
2. Myeloid Leukemia of Down syndrome (please refer to your local group for treatment alternatives)
3. Symptomatic cardiac dysfunction (CTC grade 3 or 4) and/or a Fractional Shortening at echocardiography below 29%
4. A Karnofsky performance status <40% (children * 16 years) or an Lanksy performance status of <40% (children < 16 years) before start of chemotherapy
5. Any other organ dysfunction (CTC grade 4) that will interfere with the administration of the therapy according to this protocol
6. Impaired liver function defined as > than NCI-CTC grade 1 (max 2.0 x ULN for transaminases and bilirubin)
7. History of veno-occlusive disease (VOD)
8. Hypersensitivity to gemtuzumab ozogamicin
9. Inability to potentially complete the treatment protocol for any other reason
10. Pregnant women
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 |
|---|---|
| EudraCT | EUCTR2010-018980-41-NL |
| CCMO | NL34473.078.13 |