Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Associazione Italiana Ematologia Oncologia Pediatrica
Sponsor:
Information provided by (Responsible Party):
Associazione Italiana Ematologia Oncologia Pediatrica
ClinicalTrials.gov Identifier:
NCT01226303
First received: October 20, 2010
Last updated: July 12, 2013
Last verified: July 2013
  Purpose

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).


Condition Intervention Phase
Acute Promyelocytic Leukemia
Drug: ATRA
Drug: ATRA + IDA
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

Resource links provided by NLM:


Further study details as provided by Associazione Italiana Ematologia Oncologia Pediatrica:

Primary Outcome Measures:
  • • 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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    • 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 Measures:
  • • To monitor cardiotoxicity by echocardiography [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    • To monitor cardiotoxicity by echocardiography


Estimated Enrollment: 300
Study Start Date: January 2009
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: standard risk
are defined as those patients with a WBC less than 10x10 9 /L at presentation
Drug: ATRA
see the protocol
Active Comparator: high risk
are defined as those patients whose highest treatment WBC is equal to or greater than 10x10 9 /L at presentation
Drug: ATRA + IDA
see the protocol

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01226303

Contacts
Contact: Annamaria Testi, PI 06.857951 ext +39 testi@bce.uniroma1.it
Contact: Andrea Pession, Prof 051.-6364443 ext +39 andrea.pession@unibo.it

Locations
Italy
Dipartimento di Biotecnologie Cellulari ed Ematologia Recruiting
Roma, Italy, 00161
Contact: Testi, Dr    06.857951 ext +39    testi@bce.uniroma1.it   
Principal Investigator: Annamaria Testi, Dr         
Sponsors and Collaborators
Associazione Italiana Ematologia Oncologia Pediatrica
Investigators
Principal Investigator: Annamaria Testi, Dr Associazione Italiana Ematologia Oncologia Pediatrica
  More Information

Additional Information:
No publications provided

Responsible Party: Associazione Italiana Ematologia Oncologia Pediatrica
ClinicalTrials.gov Identifier: NCT01226303     History of Changes
Other Study ID Numbers: ICC APL STUDY 01
Study First Received: October 20, 2010
Last Updated: July 12, 2013
Health Authority: Italy: National Institute of Health

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid

ClinicalTrials.gov processed this record on September 18, 2014