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EUCTR2010-018980-41 | SNCTP000002804

Internationale Studie zur Behandlung von Kindern und Jugendlichen mit Therapie-resistenter oder rezidivierender akuter myeloischer Leukämie.

Data source: BASEC (Imported from 10.12.2019), WHO (Imported from 01.12.2019)
Changed: 03.12.2019
Disease category: Leukämie

Brief description of trial (Source of data: BASEC)

Die akute myeloische Leukämie (AML) ist eine bösartige Erkrankung des blutbildenden Systems. Sie führt zu einer zum Teil massiven Vermehrung unreifer Zellen „Blasten“ im Knochenmark.
Diese Studie hat das Ziel, die Heilungsrate von Kindern mit Rückfall einer AML weiter zu verbessern. Bei dieser Studie soll festgestellt werden, ob eine einmalige zusätzliche intravenöse Gabe des Medikamentes Mylotarg® (GO) zu der gängigen intravenösen Therapie mit den Medikamenten Fludarabin, liposomalem Daunorubicin und Cytarabin, ein besseres Ansprechen auf die Therapie erzielt.
Der Ablauf der Behandlung und die notwendigen Untersuchungen sind nicht spezifisch für diese Studie, sondern bei der Durchführung jeder AML Chemotherapie erforderlich. Insgesamt besteht die Chemotherapie aus kombinierten Medikamenten (Fludarabin, Cytarabin, liposomales Daunorubicin), die über einen Zeitraum von 6 bis 8 Tagen gegeben werden (Chemotherapieblock). Danach ist jeweils eine Pause vorgesehen, in der die Medikamente wirken und die Patienten sich von den Nebenwirkungen erholen. Abhängig vom Ansprechen der Leukämie auf die Behandlung und der allfälligen Verfügbarkeit eines Blut-Stammzell- oder Knochenmarkspenders, werden insgesamt zwei oder drei Chemotherapieblöcke verabreicht.
Die Patienten erhalten entweder die Standardtherapie mit oder ohne GO. Die Zuteilung wird per Zufall entschieden.

Health conditions investigated (Source of data: BASEC)

akute myeloische Leukämie (AML) refraktär, Rezidiv

Health conditions (Source of data: WHO)

Pediatric relapsed or refractory AML
MedDRA version: 14.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) ;Therapeutic area: Diseases [C] - Cancer [C04]

Rare disease (Source of data: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Das Medikament Mylotarg® wird einmalig beim ersten Chemotherapieblock eingesetzt.

Interventions (Source of data: WHO)


Product Name: gemtuzumab ozogamicin (GO)
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: GEMTUZUMAB OZOGAMICIN
CAS Number: 220578-59-6
Other descriptive name: Mylotarg
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Criteria for participation in trial (Source of data: BASEC)

-Kinder und Jugendliche <18 Jahre beim Beginn der erste Chemotherapie, und <21 Jahre bei Beginn der Behandlung der rezidivierenden AML
-Patienten mit einem ersten Rezidiv oder refraktär AML

Exclusion criteria (Source of data: BASEC)

-Akute promyelozytische Leukämie (APL).
-Myeloische Leukämie bei Patienten mit Down Syndrom.

Inclusion/Exclusion Criteria (Source of data: WHO)

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 (including relapse after SCT) or primary refractory AML
3. Signed written informed consent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations
4. In female patients of childbearing potential pregnancy must be excluded.
5. Sexually active patients must be using two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 3 months after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (e.g. diaphragm, cervical cap, or condom) or with a spermicide.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Acute promyeloblastic leukemia (AML 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 (CTCAEv4 grade 3 or 4) and/or a Fractional Shortening at echocardiography below 29%
4. A Karnofsky performance status < 40% (children = 16 years) or an Lansky performance status of < 40% (children < 16 years) before start of chemotherapy
5. Any other organ dysfunction (CTCAEv4 grade 4) that will interfere with the administration of the therapy according to this protocol
6. Impaired liver function defined as > 3.0 x UNL for transaminases and for bilirubin
7. History of VOD
8. History hepatitis C positivity
9. Renal impairment with creatinine < 30 ml/min
10. Decompensated hemolytic anemia
11. Hypersensitivity to GO and/or other chemotherapeutic drugs
12. Inability to potentially complete the treatment protocol for any other reason
13. Pregnant or breastfeeding patients
14. Current participation in another clinical trial for the time of first course of reinduction chemotherapy

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018980-41

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2010-018980-41-DK

Further information on trial

Date trial registered

07.11.2013

Incorporation of the first participant

21.11.2013

Recruitment status

Not Recruiting

Academic title (Source of data: WHO)

International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia

Type of trial (Source of data: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Source of data: WHO)


Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: Standard chemotherapy treatment without IMP
Number of treatment arms in the trial: 2

Phase (Source of data: WHO)

Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Primary end point (Source of data: WHO)

Main Objective: Determination of the initial efficacy of GO when added to DX-FLA in the first course of reinduction chemotherapy in children with relapsed or refractory AML compared to DX-FLA only. Activity will be measured by the percentage of patients having not more than 20% blasts in the bone marrow (BM) before the second induction course.;
Secondary Objective: 1.Determine clinical outcome in both treatment arms, defined as refractory disease, complete remission rate after 2 reinduction courses, cumulative incidence of relapse, EFS and OS.
2.Incidence of treatment related mortality and toxicity of GO according to the CTCAEv4 when added to DX-FLA, in terms of mucosal toxicity, BM aplasia, liver toxicity with special respect to the development of VOD, also called SOS), short- and long-term cardiotoxicity and other adverse reactions, as compared to patients treated with DX-FLA only.
3.Identification of additional prognostic factors in pediatric relapsed AML, other than early treatment response, cytogenetics and duration of CR1.
4.Establish a diagnostic and logistic network to obtain an individual characterization of AML based on morphology, immunophenotype, type I and II mutations, signal pathway activation, and monitoring of MRD / treatment response for individualized stratification to targeted therapy within a short timeframe.
;Timepoint(s) of evaluation of this end point: day 28” (before the start of the second reinduction course) ;Primary end point(s): The percentage of bone marrow blasts after the first course of reinduction chemotherapy on day 28” (in practice anytime between day 28 and 42 after start of first reinduction chemotherapy and before the start of the second reinduction course) given as = 20% or > 20%.

Secundary end point (Source of data: WHO)


Timepoint(s) of evaluation of this end point: 1.: After second reinduction course
2.: Begin of treatment - Day 34 (or before the start of the second reinduction course)
3-4: Begin of treatment - after second reinduction course
;
Secondary end point(s): 1. Determine incidence of refractory disease, CR/CRi rates after 2 courses and efficacy (cumulative incidence of relapse, event-free survival, and overall survival) in the different study arms
2. Determine the toxicity of GO (Mylotarg®) when added to DX-FLA in terms of BM aplasia, liver toxicity including VOD, cardiotoxicity, mucosal toxicity and other adverse reactions according to CTCAEv4 which are considered to be relevant in relapsed AML and the proposed therapy when compared to treatment with DX-FLA only.
3. Identify additional prognostic factors in pediatric relapsed AML, other than early treatment response, cytogenetics and duration of CR1.
4. Provide individual biological characterization of leukemia (morphology, immunophenotype, cytogenetics, molecular genetics and activated signalling pathways), for future individualized stratification to targeted therapy.

Contact information (Source of data: WHO)

Pfizer Pharma GmbH; Deutsche José Carreras Leukämie-Stiftung e.V

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Bern, Lausanne, Zürich

Countries (Source of data: WHO)

Belgium, Czech Republic, Denmark, European Union, Germany, Hungary, Ireland, Netherlands, Serbia, Sweden

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Prof. Dr. Jean-Pierre Bourquin
+41 44 266 73 04
Jean-Pierre.Bourquin@kispi.uzh.ch

Contact for general information (Source of data: WHO)

Prof. Dr. Dirk Reinhardt
Carl-Neuberg-Str.1
Hannover Medical School
+495115326720
aml-bfm@mh-hannover.de

Contact for scientific information (Source of data: WHO)

Prof. Dr. Dirk Reinhardt
Carl-Neuberg-Str.1
Hannover Medical School
+495115326720
aml-bfm@mh-hannover.de

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Hannover Medical School

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2017-01686

Secondary ID (Source of data: WHO)

Pediatric_Relapsed_AML2010/01;2010-018980-41-BE