Clinical trial NCT04793919: Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia
Official title: Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Promyelocytic Leukemia
Lead sponsor: Associazione Italiana Ematologia Oncologia Pediatrica
Sponsor class: OTHER
First posted: 2021-03-11
Enrollment: 89
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Based on data coming from adults indicating that at least standard-risk APL patients may be cured without chemotherapy (i.e., with a treatment combining arsenic trioxide (ATO) and ATRA only) 10-12, this ICC APL 02 study was designed with the aim of validating the efficacy of a treatment combining:

* ATO and ATRA in newly diagnosed APL standard-risk (SR) children and adolescents and
* ATO, ATRA and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk (HR) children and adolescents.

Following one induction course of treatment combining ATO and ATRA +/- GO depending on risk stratification, patients will receive 4 ATO/ATRA based consolidation blocks. This is the first pediatric trial delivering a non-chemotherapy-based treatment for children with APL, being the whole treatment based on the use of ATRA, ATO (and GO in HR patients). The aim of the study is to demonstrate at least an equivalent efficacy and safety of this treatment not containing cytostatic agents compared to the standard protocols combining ATRA and chemotherapy (i.e. ICC APL Study 01).

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.

This will be an international study, comprising the most important pediatric European groups, expecting to recruit 46 and 43 patients in SR and HR arms, respectively, in 3 years. The duration of study recruitment will be 36 months with a minimum follow-up per patient of 2 years.

The evaluation of morphological CR will be carried out after induction therapy, prior to the first block of consolidation therapy. MRD results after induction will not have an impact on subsequent therapy. By contrast, MRD results after the third consolidation course will influence the subsequent treatment, MRD-positive patients being eligible to rescue treatment, including hematopoietic stem cell transplantation (HSCT). BM aspirates will be repeated after the end of therapy, and 3 months, 6 months, 9 months and 12 months after treatment discontinuation.

This is a collaborative international study in APL in children and adolescents aimed at providing information about procedures for the entry, treatment and follow-up of pediatric patients with APL. It is not intended that this document be used as an aide-memoir or guide for the treatment of other patients. Every care has been taken in its drafting, but corrections and amendments may be necessary. Before entering patients into the study, clinicians must ensure that the study has received clearance from their Local Research Ethics Committee and any other necessary body.

Eligibility criteria: 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

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

Primary outcomes:
measure: Event Free Survival (EFS) probability
timeFrame: 3 years
Secondary outcomes:
measure: Rate of hematological CR/CRi after induction
timeFrame: 5 years
measure: Rate of molecular CR/CRi after induction
timeFrame: 5 years
measure: Rate of early death during induction
timeFrame: 5 years
measure: Probability of overall survival (OS) at 3 years
timeFrame: 3 years
measure: Cumulative incidence of relapse (CIR) at 3 years
timeFrame: 3 years
measure: Incidence of hematological and non-hematological toxicity
timeFrame: 5 years
measure: Rate of molecular remission after 3 consolidation cycles
timeFrame: 5 years
measure: Assessment of PML/RARα transcription level reduction during treatment
timeFrame: 5 years
measure: Pediatric Quality of Life assessment
timeFrame: 5 years
measure: Total hospitalization days during therapy
timeFrame: 5 years
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola (Huderf)
city: Praga
country: Czechia
facility: University Hospital Motol
city: Aarhus N
country: Denmark
facility: Pediatrics and Adolescent Medicine Aarhus University Hospital
city: Bordeaux-Cedex
country: France
facility: CHU de Bordeaux - Hôpital des Enfants
city: Essen
country: Germany
facility: Universitätsklinikum Essen (AöR) Zentrum für Kinder-und Jugendmedizin Klinik für Kinderheilkunde III
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital Crumlin
city: Haifa
country: Israel
facility: Rappaport Children'S Hospital, Rambam Health Care Campus
city: San Giovanni Rotondo
country: Italy
facility: Ospedale "Casa Sollievo della Sofferenza" - UO Oncoematologia Pediatrica
state: Foggia
city: Bari
country: Italy
facility: AOU Policlinico Dipartimento di Pediatria
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII - USS Oncoematologia Pediatrica
city: Bologna
country: Italy
facility: AOU Policlinico Sant'Orsola-Malpighi - Oncologia ed Ematologia Pediatrica
city: Cagliari
country: Italy
facility: Ospedale Pediatrico Microcitemico "A.Cau", Az.Ospedaliera Brotzu - SC Oncoematologia Ped. e Patologia della coagulazione
city: Catania
country: Italy
facility: AOU Policlinico Vittorio Emanuele - UOC Ematologia ed Oncologia Pediatrica con TNO
city: Firenze
country: Italy
facility: A.O. Universitaria Meyer - DAI Oncoematologia Pediatrica
city: Genova
country: Italy
facility: IRCCS Istituto Gannina Gaslini - Dipartimento di Oncoematologia
city: Monza
country: Italy
facility: Fondazione Monza e Brianza per il Bambino e la sua Mamma (MBBM) - Ospedale San Gerardo
city: Napoli
country: Italy
facility: AORN Santobono-Pausilipon
city: Napoli
country: Italy
facility: Univerità degli Studi della Campania- Luigi Vanvitelli - Sevizio di Oncologia Pediatrica
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova - Oncoematologia Pediatrica
city: Palermo
country: Italy
facility: ARNAS Civico di Cristina e Benfratelli - UOC Oncoematologia Pediatrica
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - Oncoematologia Pediatrica
city: Pisa
country: Italy
facility: Ospedale santa Chiara - AOU Pisana, UO Oncoematologia Pediatrica
city: Roma
country: Italy
facility: Policlinico Umberto I Università "LA Sapienza" - Dip. Biotecnologie cellulari ed ematologia UOS Ematologia Pediatrica
city: Roma
country: Italy
facility: Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica - Ospedale Pediatrico "Bambino Gesù"
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino - Presidio Infantile Regina Margherita
city: Amsterdam
country: Netherlands
facility: VU medisch centrum
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitário de Coimbra - Hospital Pediátrico de Coimbra
city: Lisbon
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, E. P. E.
city: Valencia
country: Spain
facility: Valencia University Medical School University Hospital La Fe
city: Uppsala
country: Sweden
facility: Childrens hematology and oncology Uppsala University
Study officials:
affiliation: Dept. of Pediatric Hematology Oncology - Bambino Gesù Children's Hospital Rome
name: Fanco Locatelli, Prof
role: PRINCIPAL_INVESTIGATOR
References: