Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

Brief Title

Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

Official Title

Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

Brief Summary

      This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who
      are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e.
      NPM-RAR-alpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A).
    

Detailed Description

      This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who
      are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e.
      NPM-RARalpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A). APL
      is a rare disease with each national group recruiting small numbers of patients to their
      trials annually. Therefore this will be an international study expecting to recruit 60-70
      patients per annum and a total of 300 patients in 5 years. The study aims to limit the use of
      anthracyclines and stratify treatment by risk group: standard risk - WBC <10 x 109/l : high
      risk - WBC ≥10 x 109/l. All-trans retinoic acid (ATRA) is included in all phases of therapy
      and intermediate dose Ara-C (IDARAC) is given during consolidation treatment. Following one
      induction course of treatment standard risk patients have 2 consolidation blocks whilst high
      risk patients have 3 consolidation blocks.

      The PML-RARα transcript will be monitored throughout and standard risk patients with
      detectable minimal residual disease by real time quantitative reverse transcriptase
      polymerase chain reaction (RQ-PCR+) at the end of the second consolidation block will receive
      a third consolidation block identical to high risk patients. Patients who are RQ-PCR+ for
      PML-RARα after completion of the third block of consolidation therapy will be candidates for
      refractory/relapse treatment, but will remain on study. Refractory/relapsed patients who
      remain RQ-PCR+ for PML-RARα will be candidates for allogeneic bone marrow transplantation
      (allo-BMT), whilst those who become RQ-PCR- for PML-RARα will have individualised treatment
      with ongoing MRD monitoring.

      These study guidelines are intended to describe a collaborative international study in APL in
      children and adolescents and to provide information about procedures for the entry, treatment
      and follow-up of patients. It is not intended that these guidelines 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 3

Study Type

Interventional

Primary Outcome

• to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity

Secondary Outcome

 • To monitor cardiotoxicity by echocardiography

Condition

Acute Promyelocytic Leukemia

Intervention

ATRA

Study Arms / Comparison Groups

 standard risk

Description:  are defined as those patients with a WBC less than 10x10 9 /L at presentation

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

300

Start Date

January 2009

Completion Date

December 2018

Primary Completion Date

June 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a clinical diagnosis of initial APL and subsequently confirmed to have
             PML-RARα, NPM1-RARα or NUMA-RARα fusion. Whilst this study is only for ATRA-sensitive
             APL, APL is a hematological emergency and ATRA should be commenced as soon as the
             diagnosis is suspected. Study entry should not wait until the diagnosis of APL has
             been confirmed molecularly or cytogenetically

          -  Less than 21 years of age at initial diagnosis (for AIEOP, see appendix A)

          -  Considered suitable for anthracycline-based chemotherapy

          -  Written informed consent available

          -  Females of childbearing age must have a negative pregnancy test and subsequently must
             attempt to avoid pregnancy

        Exclusion Criteria:

          -  Patients with a clinical diagnosis of APL but subsequently found to have PLZF-RARα
             fusion or lacking PML-RARα, NPM-RARα or NuMA-RARα rearrangement should be withdrawn
             from the study and treated on an alternative protocol.

          -  Refractory/relapsed APL (the guidelines in this protocol for that subgroup are
             intended for patients treated from initial diagnosis according to this protocol)

          -  Concurrent active malignancy

          -  Pregnant or lactating

          -  Physician and patient/guardian think that intensive chemotherapy is not an appropriate
             treatment option

          -  Patients who have received alternative chemotherapy for 7 days or longer without ATRA
             for any reason (either APL not initially suspected or ATRA not available).
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Annamaria Testi, Dr, 06.857951, [email protected]

Location Countries

Italy

Location Countries

Italy

NCT ID

NCT01226303

Organization ID

ICC APL STUDY 01

Responsible Party

Sponsor

Study Sponsor

Associazione Italiana Ematologia Oncologia Pediatrica

Study Sponsor

Annamaria Testi, Dr, Principal Investigator, Associazione Italiana Ematologia Oncologia Pediatrica

Verification Date

July 2016