Trial Information

ALL-REZ BFM 2002: Protocol for the Treatment of Children With Relapsed Acute Lymphoblastic Leukemia

The study is based on the results of five consecutive trials performed by the ALL-REZ BFM
study group since 1983. Thus the study meets the criteria of evidence-based therapy, which
has been developed over nearly 20 years. Multi-agent chemotherapy in short intensive
courses, which are separated by treatment-free intervals, has proved to be a successful form
of induction and consolidation therapy. It is followed by preventative (or therapeutic)
cranial irradiation and continuation therapy. A number of risk factors, particularly the
time of relapse, site of relapse, and the ALL immunophenotype, allow the stratification of
patients into a group that has an acceptable prognosis after treatment with chemotherapy
alone and a second group that has a high risk of subsequent recurrence following the
achievement of a second remission. The latter group requires further intensification of
consolidation therapy by allogenic stem cell transplantation (SCT). To date, the indication
for SCT has remained unclear for a large and heterogeneous group of patients with an
intermediate prognosis. During the precursor study ALL-REZ BFM 96, however, the amount of
minimal residual disease (MRD) determined quantitatively with clonal molecular markers after
the second induction therapy element was shown to be a highly significant predictor of
relapse-free survival.

The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower
dosed and less intensive, but continuous consolidation therapy with conventional therapy
administered in treatment blocks. Outcome measures are the reduction of MRD, event-free and
overall survival, and the toxicity associated with each treatment strategy.

The secondary objectives include an improvement of the prognosis in the intermediate risk
group using the stratification in treatment arms with and without allogenic SCT based on the
MRD result after the second treatment element of induction therapy. An additional aim is to
improve the remission induction rate in all groups by increasing the treatment intensity
during induction. This is achieved by shortening the intervals between treatment blocks in
keeping with the principles of guiding therapy as defined in the protocol. A series of
biological companion studies aims to advance our understanding of the disorder and to
establish novel prognostic factors that will allow a risk-adapted therapy.