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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

From the Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children’s Hospital, Boston, MA; Children’s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children’s National Medical Center, Washington, DC; Children’s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal, Canada; National Cancer Institute, Bethesda, MD; Tomorrow’s Children’s Institute, Hackensack, NJ; Vanderbilt Children’s Hospital, Nashville, TN

Address reprint requests to Stacey L. Berg, MD, Texas Children's Cancer Center, 6621 Fannin St, MC3-3320, Houston, TX 77030; e-mail: sberg{at}txccc.org

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/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 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.

This study originated as a Pediatric Oncology Group/Children’s Cancer Group intergroup study.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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