Phase II Study of Nelarabine (compound 506U78) in Children and Young Adults With Refractory T-Cell Malignancies: A Report From the Children’s Oncology Group

Purpose Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. Patients and Methods We performed a phase II study with patients stratified as follows: stratum 1: ≥ 25% bone marrow blasts in first relapse; stratum 2: ≥ 25% bone marrow blasts in ≥ second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m 2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m 2 /d for strata 1 and two patients and 400 mg/m 2 /d for strata 3 and four patients. Results We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of ≥ grade 3 neurologic adverse events in 27 patients (18% of patients). Conclusion Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.