Trial Information

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-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.