Trial Information

Phase 2 Study Evaluating the Efficacy of Rituximab Plus Modified VPDL for Newly Diagnosed CD20-Positive Philadelphia-Negative Adult Acute Lymphoblastic Leukemia

According to the recent results on the outcome of escalated daunorubicin-based protocol for
adult ALL which has been performed by 'Adult ALL Working Party of the Korean Society of
Hematology' (data were announced at 2010 Annual Meeting of ASCO, Chicago, IL), CR rate of
90.6% was satisfactory, but the 2-year / 3-year disease-free survival (DFS) were
disappointing (43.6% and 39.9%, respectively), which means that the adequate post-remission
therapy to control minimal residual disease after the achievement of CR is very important to
improve the outcome of adult ALL.

Allogeneic hematopoietic cell transplantation (AlloHCT) is recommended as a post-remission
therapy for patients with adult ALL, and reduced intensity conditioning has been tried to
decrease TRM rate. However, many patients received consolidation chemotherapy rather than
alloHCT owing to the absence of HLA-matched donor, limitation of age, and combined
comorbidities (among 190 patients who have been included in our previously-mentioned study,
only 52.3% received alloHCT).

Recently, stagnation in the treatment of adult ALL appears to be reached, maybe due to a
borderline for further intensification of chemotherapeutic dose. Dose-escalation strategy
has many difficulties in adoption for the treatment of adult ALL in terms of increased
morbidity and mortality, not to mention the efficacy of such strategies. New, preferably
non-chemotherapy approaches (maybe targeted therapy) are therefore urgently required.

For Ph(+) ALL, the introduction of BCR/ABL tyrosine kinase inhibitor has improved the
treatment outcome with tolerable toxicities. Applying a similar strategy to Ph(-) ALL,
targeting leukemia surface antigens with monoclonal antibodies is another promising
strategy.

CD 20 expression of at least 20% has been known to be found in 22-48% of pre-B ALL, and
appears to be associated with a poor prognosis, although there are controversies in
pediatric patients. Based on the significant improvement of the outcome in B-cell NHL,
preliminary data regarding the use of rituximab in frontline therapy for CD20-positive
precursor B-cell ALL suggest its use may be beneficial. Especially, monoclonal antibodies
are thought to be more effective when combined with chemotherapy and treated in the state of
minimal residual disease, which suggests the interest of evaluating rituximab combined to
current chemotherapy of adult ALL. Recent data on the efficacy of rituximab-combined
chemotherapy showed that rates of CR and OS were superior with the modified hyperCVAD and
rituximab regimens compared with standard hyper-CVAD (70% versus 38%, p<0.001) in younger
(age < 60 years) CD20-positive subset, although it was an analysis of different patient
groups who were treated with various regimen5.