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-RAR-alpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A).
Title
- Brief Title: Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia
- Official Title: Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia
Clinical Trial IDs
- ORG STUDY ID:
ICC APL STUDY 01
- NCT ID:
NCT01226303
Conditions
- Acute Promyelocytic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
ATRA | | standard risk |
ATRA + IDA | | high risk |
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).
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.
Trial Arms
Name | Type | Description | Interventions |
---|
standard risk | Experimental | are defined as those patients with a WBC less than 10x10 9 /L at presentation | |
high risk | Active Comparator | are defined as those patients whose highest treatment WBC is equal to or greater than 10x10 9 /L at presentation | |
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).
Maximum Eligible Age: | 21 Years |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | • 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 |
Safety Issue: | |
Description: | • 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
Measure: | • To monitor cardiotoxicity by echocardiography |
Time Frame: | 5 years |
Safety Issue: | |
Description: | • To monitor cardiotoxicity by echocardiography |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | Associazione Italiana Ematologia Oncologia Pediatrica |
Last Updated
January 26, 2017