Brief description of trial (Data source: 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(Data source: BASEC)
akute myeloische Leukämie (AML) refraktär, Rezidiv
Health conditions
(Data source: WHO)
Pediatric relapsed or refractory AML
MedDRA version: 14.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04]
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
Das Medikament Mylotarg® wird einmalig beim ersten Chemotherapieblock eingesetzt.
Interventions
(Data source: 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
(Data source: 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
(Data source: BASEC)
-Akute promyelozytische Leukämie (APL).
-Myeloische Leukämie bei Patienten mit Down Syndrom.
Inclusion/Exclusion Criteria
(Data source: 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 trial
Date trial registered
Nov 7, 2013
Incorporation of the first participant
Nov 21, 2013
Recruitment status
Not Recruiting
Academic title
(Data source: WHO)
International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia
Type of trial
(Data source: WHO)
Interventional clinical trial of medicinal product
Design of the trial
(Data source: 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
(Data source: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Primary end point
(Data source: 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.
;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%.;Timepoint(s) of evaluation of this end point: day 28” (before the start of the second reinduction course)
Secundary end point
(Data source: WHO)
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.
;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
Contact information
(Data source: WHO)
Pfizer Pharma GmbH; Deutsche José Carreras Leukämie-Stiftung e.V
Trial results
(Data source: WHO)
Results summary
International randomized phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
Bern, Lausanne, Zurich
Countries
(Data source: WHO)
Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Belgium, Czech Republic, Denmark, European Union, Germany, Hungary, Ireland, Netherlands, Serbia, Sweden
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
Prof. Dr. Jean-Pierre Bourquin
+41 44 266 73 04
Jean-Pierre.Bourquin@kispi.uzh.ch
Contact for general information
(Data source: WHO)
Prof. Dr. Dirk Reinhardt
Carl-Neuberg-Str.1
Hannover Medical School
+495115326720
aml-bfm@mh-hannover.de
Contact for scientific information
(Data source: WHO)
Prof. Dr. Dirk Reinhardt
Carl-Neuberg-Str.1
Hannover Medical School
+495115326720
aml-bfm@mh-hannover.de
Authorisation by the ethics committee (Data source: BASEC)
Name of the authorising ethics committee (for multicentre studies only the lead committee)
Kantonale
Ethikkommission Zürich
Date of authorisation by the ethics committee
13.03.2018
Further trial identification numbers
Trial identification number of the ethics committee (BASEC-ID)
(Data source: BASEC)
2017-01686
Secondary ID (Data source: WHO)
Pediatric_Relapsed_AML2010/01
2010-018980-41-BE
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