Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

Brief Title

Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

Official Title

Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Event Free Survival (EFS) probability

Secondary Outcome

 Rate of hematological CR/CRi after induction

Condition

Acute Promyelocytic Leukemia

Intervention

Mylotarg

Study Arms / Comparison Groups

 Standard Risk (SR)

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

89

Start Date

October 9, 2019

Completion Date

October 10, 2024

Primary Completion Date

October 10, 2022

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
      

Gender

All

Ages

N/A - 18 Years

Accepts Healthy Volunteers

No

Contacts

Fanco Locatelli, Prof, 0039 051 2144667, [email protected]

Location Countries

Belgium

Location Countries

Belgium

NCT ID

NCT04793919

Organization ID

ICC APL STUDY 02

Secondary IDs

2017-002383-40

Responsible Party

Sponsor

Study Sponsor

Associazione Italiana Ematologia Oncologia Pediatrica

Study Sponsor

Fanco Locatelli, Prof, Principal Investigator, Dept. of Pediatric Hematology Oncology - Bambino Gesù Children's Hospital Rome

Verification Date

August 2022