Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia

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).

Study Overview

• Status: Unknown
• Conditions: Acute Promyelocytic Leukemia
• Intervention / Treatment: Drug: ATRA; Drug: ATRA + IDA

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 Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Annamaria Testi, PI; Phone Number: +39 06.857951; Email: testi@bce.uniroma1.it
• Study Contact Backup: Name: Andrea Pession, Prof; Phone Number: +39 051.-6364443; Email: andrea.pession@unibo.it

Study Locations

• Italy
  • Roma, Italy, 00161
    • Recruiting
    • Dipartimento di Biotecnologie Cellulari ed Ematologia
    • Contact: Testi, Dr; Phone Number: +39 06.857951; Email: testi@bce.uniroma1.it
    • Principal Investigator: Annamaria Testi, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• 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	• 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	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• To monitor cardiotoxicity by echocardiography	• To monitor cardiotoxicity by echocardiography	5 years

Collaborators and Investigators

• Sponsor: Associazione Italiana Ematologia Oncologia Pediatrica
• Investigators: Principal Investigator: Annamaria Testi, Dr, Associazione Italiana Ematologia Oncologia Pediatrica

Publications and helpful links

Helpful Links

• Italian association of Pediatric Hematology and Oncology

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: October 20, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimate): October 22, 2010

Study Record Updates

• Last Update Posted (Estimate): January 26, 2017
• Last Update Submitted That Met QC Criteria: January 25, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: ICC APL STUDY 01