Pediatric relapsed or refractory acute myeloid leukemia (AML) Cancer Myeloid leukemia
Conditions
Interventions
The aim of this study is to answer a randomized study question: can the response to the first reinduction chemotherapy block be improved by the addition of GO to the standard therapy?
Fludarabine dosis: 30 mg/m2/day, day 1-5
Cytarabine dosis: 2000 mg/m2/day, day 1-5)
Experimental Arm: DX-FLA + GO (Triple IT: Cytarabine, Methotraxate, Prednisolone i.th in age related dosis on day 0, liposomal daunorubicine
Cytarabine dosis: 2000 mg/m2/day, day 1-5
Gemtuzumab ozogomicin dosis: 4.5 mg/m2, day 6)
Subsequent therapy depends on the response to the first block:
>20% blasts off protocol
=20% blasts
Cytarabine dosis: 2000mg/m2/day, day 1-5)
Consolidation high intensity (Triple IT: Cytarabine, Methotraxate, Prednisolone i.th in age related dosis on day 1
Cytarabine dosis: 500 mg/m2/day, day 1-4
Etoposide dosis: 100 mg/m2/day, day 1-5)
or
Consolidation low intensity (Triple IT: Cytarabine, Methotraxate, Prednisolone i.th in age related dosis on day 1
Cytarabine dosis: 75 mg/m2/day, day 1-4 and 15-18 s.c.
Thioguanine dosis: 100 mg/m2/day, max. 4 weeks oral dose)
Stem cell transplantation (SCT)
Total duration of therapy will be up to three months. Follow-up duration wil
Sponsors
Hannover Medical School represented by Hannover Clinical Trial Center (HCTC)
Eligibility
Sex/Gender
All
Inclusion criteria
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.
Exclusion criteria
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 3.0 x UNL for transaminases and for bilirubin 7. History of VOD 8. History of 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The early treatment response will be determined by morphological and flow cytometric examination of the BM sampled at day 28 (in practice anytime between day 28 and 42 after start of first reinduction chemotherapy). If the BM shows 20% of leukemic blasts or less, the response is good. If the BM shows > 20% leukemic blasts, the response is poor. Event-free, disease-free and overall survival and AML toxicity rates will be evaluated. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Determination of the incidence of refractory disease, CR/CRi rates after two courses and long-term efficacy (cumulative incidence of relapse, event-free survival, and overall survival) in the different study arms 2. Determination of 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. Identification of additional prognostic factors in pediatric relapsed AML, other than early treatment response, cytogenetics and duration of first remission 4. Providing of individual biological characterization of leukemia (morphology, immunophenotype, cytogenetics, molecular genetics and activated signalling pathways), for future individualized stratification to targeted therapy | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Netherlands, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom
Outcome results
None listed