Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

Registration Number
NCT04793919
Lead Sponsor
Associazione Italiana Ematologia Oncologia Pediatrica
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.
...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
89
Inclusion Criteria
  • Newly diagnosed APL confirmed by the presence of PML/RARα fusion gene
  • Age <18 years
  • Written informed consent by parents or legal guardians
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Exclusion Criteria
  • Patients with a clinical diagnosis of APL but subsequently found to lack PML/RARα rearrangement should be withdrawn from the study and treated on an alternative protocol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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High Risk (HR)MylotargPatient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
Standard Risk (SR)Arsenic TrioxidePatient with APL and WBC less than 10x10e9/L at presentation before start treatment
High Risk (HR)Arsenic TrioxidePatient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
Standard Risk (SR)All-trans retinoic acidPatient with APL and WBC less than 10x10e9/L at presentation before start treatment
High Risk (HR)All-trans retinoic acidPatient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation
Primary Outcome Measures
NameTimeMethod
Event Free Survival (EFS) probability3 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
NameTimeMethod
Rate of hematological CR/CRi after induction5 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 years3 years

To evaluate the rate of overall survival

Cumulative incidence of relapse (CIR) at 3 years3 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 toxicity5 years

Incidence of treatment-related hematological and non-hematological toxicity assessed by CTCAE v4.0

Total hospitalization days during therapy5 years

Number of total hospitalization days during the treatment.

Rate of molecular CR/CRi after induction5 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 induction5 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 cycles5 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 treatment5 years

To evaluate the reduction of PML/RARα fusion transcript in bone marrow by means of RQ-PCR during treatment.

Pediatric Quality of Life assessment5 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

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