Nelarabine in combination with intensive modified BFM AALL00P2: A pilot study for the treatment of high risk T-ALL a report from the Children’s Oncology Group

Abstract

10002 Background: Nelarabine has substantial clinical activity in relapsed T-ALL, but has been associated with significant neurotoxicity. Historically, children with high risk T-ALL, based on prednisone response or high-end induction MRD, have fared poorly with less than 50% cured with chemotherapy leading some groups to recommend allogeneic stem cell transplant in first remission for these patients. AALL00P2 was a two-stage pilot study designed to assess the feasibility and safety of adding Nelarabine to an intensive modified BFM regimen in children with newly-diagnosed T-ALL with high risk features. Methods: Ninety-two patients (89 eligible) were accrued from April 2001 to October 2005. In stage 1, patients with a slow early response (SER), defined as > 1000 peripheral blood blasts on day 8 of a prednisone prephase or MRD >1% at day 36 of induction therapy, were assigned to receive chemotherapy that included 5-day courses of Nelarabine at 400mg/m2/day; other patients received chemotherapy without Nelarabine. In stage 2, all patients received therapy with six courses of Nelarabine, at either 650mg/m2/day (SER patients, n=10) or 400mg/m2/day (others, n=51). Results: The 3-year EFS for stage 1 SER patients assigned to Nelarabine 400mg/m2 is 75% + 13% (n= 12), versus 75% + 11% for 16 good responders receiving no Nelarabine. Three-year EFS for all NCI high risk patients receiving Nelarabine 400mg/m2 (n=50) is 85%; 650mg/m2 (n=10) is 70%; and for no Nelarabine (n=13) 69%. There were no differences in either targeted or non-targeted toxicities among patients treated ± Nelarabine (Dunsmore et. al, Blood 108: 528a, 2006). Conclusions: In this pilot study, T-ALL patients with high-risk features and previously very poor outcomes, attained a 3-year EFS of >70% with intensive chemotherapy plus Nelarabine, without excess toxicity, and SER patients appeared to fare as well as good responding patients. These preliminary results have led the COG to randomize patients with T-ALL to intensive chemotherapy ± Nelarabine. AALL0434 will define the role of Nelarabine in patients with newly diagnosed T-ALL. No significant financial relationships to disclose.