Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia
- Conditions
- Interventions
- Registration Number
- NCT04793919
- Brief Summary
The trial is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR-positive for the PML-RARα transcript and less than 18 years of age.
- Detailed Description
Acute promyelocytic leukemia (APL) in children has become a highly curable disease with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy with an overall remission rates equal to or higher than 98% and cure rates now exceeding 80% 1-9.
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Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 89
- Newly diagnosed APL confirmed by the presence of PML/RARα fusion gene
- Age <18 years
- Written informed consent by parents or legal guardians
- Patients with a clinical diagnosis of APL but subsequently found to lack PML/RARα rearrangement should be withdrawn from the study and treated on an alternative protocol
- Significant liver dysfunction (bilirubin serum levels >3 mg/dL, ALT/AST serum levels greater than 5 times the normal values)
- Creatinine serum levels >2 times the normal value for age
- Significant arrhythmias, EKG abnormalities (*see below), other cardiac contraindications (L-FEV <50% or LV-FS <28%)
- Neuropathy
- Concurrent active malignancy
- Uncontrolled life-threatening infections
- Pregnant or lactating female
- Patients who had received alternative therapy (APL not initially suspected; ATRA and/or ATO not available
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High Risk (HR) Mylotarg Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation Standard Risk (SR) Arsenic Trioxide Patient with APL and WBC less than 10x10e9/L at presentation before start treatment High Risk (HR) Arsenic Trioxide Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation Standard Risk (SR) All-trans retinoic acid Patient with APL and WBC less than 10x10e9/L at presentation before start treatment High Risk (HR) All-trans retinoic acid Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) probability 3 years SR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in newly diagnosed APL standard-risk children and adolescents HR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO), all-trans retinoic acid (A...
- Secondary Outcome Measures
Name Time Method Rate of hematological CR/CRi after induction 5 years To evaluate the rate of hematological Complete Remission (CR) (defined as bone marrow regenerating normal hematopoietic cells and containing \< 5% blast cells by morphology, with ANC in peripheral blood \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L) and Complete Remission with incomplete hematologic recovery (CRi) (defined as CR except that peripheral...
Probability of overall survival (OS) at 3 years 3 years To evaluate the rate of overall survival
Cumulative incidence of relapse (CIR) at 3 years 3 years To evaluate the cumulative incidence of hematological relapse (defined as reappearance of promyeloblasts/abnormal promyelocytes \> 5% in the bone marrow) and molecular relapse (defined as reappearance of PML/RARα fusion transcript in two successive samples taken at least 2 weeks apart in patients previously in molecular remission).
Incidence of hematological and non-hematological toxicity 5 years Incidence of treatment-related hematological and non-hematological toxicity assessed by CTCAE v4.0
Total hospitalization days during therapy 5 years Number of total hospitalization days during the treatment.
Rate of molecular CR/CRi after induction 5 years To evaluate the rate of molecular CR/CRi (defined as the absence of PML/RARα fusion transcript in bone marrow assessed by RQ-PCR, with an assay sensitivity of at least 10\^-4).
Rate of early death during induction 5 years To evaluate the rate of early death during induction (defined as any death occurring within 14 days from diagnosis from any cause).
Rate of molecular remission after 3 consolidation cycles 5 years To evaluate the rate of molecular remission (defined as the absence of PML/RARα fusion transcript in bone marrow assessed by RQ-PCR, with an assay sensitivity of at least 10\^-4) after 3 consolidation cycles.
Assessment of PML/RARα transcription level reduction during treatment 5 years To evaluate the reduction of PML/RARα fusion transcript in bone marrow by means of RQ-PCR during treatment.
Pediatric Quality of Life assessment 5 years Pediatric Quality of life assessed by PedsQoL questionnaire, in the questionnaire there is a list of things that might be a problem for the child. The minimum value is 0 (never a problem) - maximum value 4 (almost always problem)
Trial Locations
- Locations (31)
Instituto Português de Oncologia do Porto Francisco Gentil, E. P. E.
🇵🇹Porto, Portugal
AOU Policlinico Dipartimento di Pediatria
🇮🇹Bari, Italy
Ospedale Papa Giovanni XXIII - USS Oncoematologia Pediatrica
🇮🇹Bergamo, Italy
IRCCS Istituto Gannina Gaslini - Dipartimento di Oncoematologia
🇮🇹Genova, Italy
Azienda Ospedaliera di Padova - Oncoematologia Pediatrica
🇮🇹Padova, Italy
Rappaport Children'S Hospital, Rambam Health Care Campus
🇮🇱Haifa, Israel
AOU Policlinico Vittorio Emanuele - UOC Ematologia ed Oncologia Pediatrica con TNO
🇮🇹Catania, Italy
Fondazione Monza e Brianza per il Bambino e la sua Mamma (MBBM) - Ospedale San Gerardo
🇮🇹Monza, Italy
Univerità degli Studi della Campania- Luigi Vanvitelli - Sevizio di Oncologia Pediatrica
🇮🇹Napoli, Italy
ARNAS Civico di Cristina e Benfratelli - UOC Oncoematologia Pediatrica
🇮🇹Palermo, Italy
Valencia University Medical School University Hospital La Fe
🇪🇸Valencia, Spain
A.O. Universitaria Meyer - DAI Oncoematologia Pediatrica
🇮🇹Firenze, Italy
Universitätsklinikum Essen (AöR) Zentrum für Kinder-und Jugendmedizin Klinik für Kinderheilkunde III
🇩🇪Essen, Germany
CHU de Bordeaux - Hôpital des Enfants
🇫🇷Bordeaux-Cedex, France
University Hospital Motol
🇨🇿Praga, Czechia
VU medisch centrum
🇳🇱Amsterdam, Netherlands
AORN Santobono-Pausilipon
🇮🇹Napoli, Italy
Policlinico Umberto I Università "LA Sapienza" - Dip. Biotecnologie cellulari ed ematologia UOS Ematologia Pediatrica
🇮🇹Roma, Italy
Ospedale santa Chiara - AOU Pisana, UO Oncoematologia Pediatrica
🇮🇹Pisa, Italy
AOU Città della Salute e della Scienza di Torino - Presidio Infantile Regina Margherita
🇮🇹Torino, Italy
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica - Ospedale Pediatrico "Bambino Gesù"
🇮🇹Roma, Italy
Childrens hematology and oncology Uppsala University
🇸🇪Uppsala, Sweden
Hôpital Universitaire des Enfants Reine Fabiola (Huderf)
🇧🇪Brussels, Belgium
Pediatrics and Adolescent Medicine Aarhus University Hospital
🇩🇰Aarhus N, Denmark
Our Lady's Children's Hospital Crumlin
🇮🇪Dublin, Ireland
Ospedale "Casa Sollievo della Sofferenza" - UO Oncoematologia Pediatrica
🇮🇹San Giovanni Rotondo, Foggia, Italy
AOU Policlinico Sant'Orsola-Malpighi - Oncologia ed Ematologia Pediatrica
🇮🇹Bologna, Italy
Ospedale Pediatrico Microcitemico "A.Cau", Az.Ospedaliera Brotzu - SC Oncoematologia Ped. e Patologia della coagulazione
🇮🇹Cagliari, Italy
Fondazione IRCCS Policlinico San Matteo - Oncoematologia Pediatrica
🇮🇹Pavia, Italy
Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
🇵🇹Lisbon, Portugal
Centro Hospitalar Universitário de Coimbra - Hospital Pediátrico de Coimbra
🇵🇹Coimbra, Portugal