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.

Abstract

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: > or = 25% bone marrow blasts in first relapse; stratum 2: > or = 25% bone marrow blasts in > or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 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/m2/d for strata 1 and two patients and 400 mg/m2/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 > or = 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.

• Authors: Stacey L Berg, Susan M Blaney, Meenakshi Devidas, Tom A Lampkin, Anthony Murgo, Mark Bernstein, Amy Billett, Joanne Kurtzberg, Greg Reaman, Paul Gaynon, James Whitlock, Mark Krailo, Michael B Harris, Children's Oncology Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 15 Pg. 3376-82 (May 20 2005) ISSN: 0732-183X [Print] United States
• PMID: 15908649 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Arabinonucleosides
• nelarabine

Topics

• Adolescent
• Adult
• Arabinonucleosides (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infant
• Infusions, Intravenous
• Leukemia, T-Cell (drug therapy, mortality, pathology)
• Male
• Maximum Tolerated Dose
• Neoplasm Staging
• Recurrence
• Risk Assessment
• Survival Rate
• Treatment Outcome