Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

NCT ID: NCT04793919

Last Updated: 2024-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

89 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-09

Study Completion Date

2027-10-10

Brief Summary

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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

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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.

Conditions

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Acute Promyelocytic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Risk (SR)

Patient with APL and WBC less than 10x10e9/L at presentation before start treatment

Group Type ACTIVE_COMPARATOR

Arsenic Trioxide

Intervention Type DRUG

See the protocol

All-trans retinoic acid

Intervention Type DRUG

See the protocol

High Risk (HR)

Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation

Group Type EXPERIMENTAL

Mylotarg

Intervention Type DRUG

See the protocol

Arsenic Trioxide

Intervention Type DRUG

See the protocol

All-trans retinoic acid

Intervention Type DRUG

See the protocol

Interventions

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Mylotarg

See the protocol

Intervention Type DRUG

Arsenic Trioxide

See the protocol

Intervention Type DRUG

All-trans retinoic acid

See the protocol

Intervention Type DRUG

Other Intervention Names

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GO ATO ATRA

Eligibility Criteria

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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
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Associazione Italiana Ematologia Oncologia Pediatrica

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fanco Locatelli, Prof

Role: PRINCIPAL_INVESTIGATOR

Dept. of Pediatric Hematology Oncology - Bambino Gesù Children's Hospital Rome

Locations

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Hôpital Universitaire des Enfants Reine Fabiola (Huderf)

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Motol

Prague, , Czechia

Site Status NOT_YET_RECRUITING

Pediatrics and Adolescent Medicine Aarhus University Hospital

Aarhus N, , Denmark

Site Status NOT_YET_RECRUITING

CHU de Bordeaux - Hôpital des Enfants

Bordeaux, , France

Site Status RECRUITING

Universitätsklinikum Essen (AöR) Zentrum für Kinder-und Jugendmedizin Klinik für Kinderheilkunde III

Essen, , Germany

Site Status NOT_YET_RECRUITING

Our Lady's Children's Hospital Crumlin

Dublin, , Ireland

Site Status NOT_YET_RECRUITING

Rappaport Children'S Hospital, Rambam Health Care Campus

Haifa, , Israel

Site Status NOT_YET_RECRUITING

Ospedale "Casa Sollievo della Sofferenza" - UO Oncoematologia Pediatrica

San Giovanni Rotondo, Foggia, Italy

Site Status RECRUITING

AOU Policlinico Dipartimento di Pediatria

Bari, , Italy

Site Status NOT_YET_RECRUITING

Ospedale Papa Giovanni XXIII - USS Oncoematologia Pediatrica

Bergamo, , Italy

Site Status NOT_YET_RECRUITING

AOU Policlinico Sant'Orsola-Malpighi - Oncologia ed Ematologia Pediatrica

Bologna, , Italy

Site Status RECRUITING

Ospedale Pediatrico Microcitemico "A.Cau", Az.Ospedaliera Brotzu - SC Oncoematologia Ped. e Patologia della coagulazione

Cagliari, , Italy

Site Status RECRUITING

AOU Policlinico Vittorio Emanuele - UOC Ematologia ed Oncologia Pediatrica con TNO

Catania, , Italy

Site Status RECRUITING

A.O. Universitaria Meyer - DAI Oncoematologia Pediatrica

Florence, , Italy

Site Status NOT_YET_RECRUITING

IRCCS Istituto Gannina Gaslini - Dipartimento di Oncoematologia

Genova, , Italy

Site Status RECRUITING

Fondazione Monza e Brianza per il Bambino e la sua Mamma (MBBM) - Ospedale San Gerardo

Monza, , Italy

Site Status RECRUITING

AORN Santobono-Pausilipon

Napoli, , Italy

Site Status RECRUITING

Univerità degli Studi della Campania- Luigi Vanvitelli - Sevizio di Oncologia Pediatrica

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliera di Padova - Oncoematologia Pediatrica

Padua, , Italy

Site Status NOT_YET_RECRUITING

ARNAS Civico di Cristina e Benfratelli - UOC Oncoematologia Pediatrica

Palermo, , Italy

Site Status NOT_YET_RECRUITING

Fondazione IRCCS Policlinico San Matteo - Oncoematologia Pediatrica

Pavia, , Italy

Site Status RECRUITING

Ospedale santa Chiara - AOU Pisana, UO Oncoematologia Pediatrica

Pisa, , Italy

Site Status NOT_YET_RECRUITING

Policlinico Umberto I Università "LA Sapienza" - Dip. Biotecnologie cellulari ed ematologia UOS Ematologia Pediatrica

Roma, , Italy

Site Status NOT_YET_RECRUITING

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica - Ospedale Pediatrico "Bambino Gesù"

Roma, , Italy

Site Status RECRUITING

AOU Città della Salute e della Scienza di Torino - Presidio Infantile Regina Margherita

Torino, , Italy

Site Status RECRUITING

VU medisch centrum

Amsterdam, , Netherlands

Site Status NOT_YET_RECRUITING

Centro Hospitalar Universitário de Coimbra - Hospital Pediátrico de Coimbra

Coimbra, , Portugal

Site Status NOT_YET_RECRUITING

Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE

Lisbon, , Portugal

Site Status NOT_YET_RECRUITING

Instituto Português de Oncologia do Porto Francisco Gentil, E. P. E.

Porto, , Portugal

Site Status NOT_YET_RECRUITING

Valencia University Medical School University Hospital La Fe

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Childrens hematology and oncology Uppsala University

Uppsala, , Sweden

Site Status NOT_YET_RECRUITING

Countries

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Belgium Czechia Denmark France Germany Ireland Israel Italy Netherlands Portugal Spain Sweden

Central Contacts

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AIEOP

Role: CONTACT

0039 051 2144667

Facility Contacts

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Laurence Dedeken, MD

Role: primary

+324772678

Lucie Sramkova, MD

Role: primary

22443 6401 ext. +420

Henrik Hasle, Prof.

Role: primary

Stéphane Ducassou, MD PhD

Role: primary

0557820440

Aurore Capelli

Role: backup

0557820877

Dirk Reinhardt, Prof

Role: primary

49-(0)201 1723-3784

Owen P. Smith, Prof

Role: primary

003531-4096720

NIRA ARAD-COHEN, MD

Role: primary

+972-50-206-1181

Saverio Ladogana, Dr

Role: primary

Massimo Provenzi, Dr

Role: primary

Andrea Pession, Prof

Role: primary

Rosamaria Mura, Dr

Role: primary

Luca Lo Nigro, Dr

Role: primary

Tommaso Casini, Dr

Role: primary

Concetta Micalizzi, Dr

Role: primary

Carmelo Rizzari, Dr

Role: primary

Giuseppe Menna, Dr

Role: primary

Francesca Rossi, Prof

Role: primary

Alessandra Biffi, Prof

Role: primary

Paolo D'Angelo, Dr

Role: primary

Marco Zecca, Dr

Role: primary

Gabriella Casazza, Dr

Role: primary

Anna Maria Testi, Dr

Role: primary

Valentina Cirillo, Dr

Role: primary

Franca Fagioli, Prof

Role: primary

Gertjan Kasper, Prof. dr.

Role: primary

Manuel Brito, Dr.

Role: primary

Ximo Duarte, Dr.

Role: primary

Vítor Costa, Dr.

Role: primary

Miguel A. Sanz, MD

Role: primary

Josefine Palle, MD

Role: primary

Other Identifiers

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2017-002383-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ICC APL STUDY 02

Identifier Type: -

Identifier Source: org_study_id

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