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

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.

Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T‐cell lymphoblastic leukaemia and lymphoma

“…This is consistent with data on the increased difficulty of getting relapsed LL patients into a CR2 (Burkhardt et al, 2009). Although our numbers are small, the response rate appeared to be better than for AraG alone in a similar refractory population (Berg et al, 2005).…”

“…In a combined adult and paediatric phase 1 study, patients with T-cell ALL had a response rate of 54%; although T-cell LL patients only had a 13% response rate . A single agent Phase II paediatric trial in children with refractory T-cell haematological malignancies showed a 48% CR2 rate and a 23% CR3 rate for T-cell ALL (Berg et al, 2005). As a result of toxicity, the dose of AraG had to be de-escalated from the maximal tolerated dose found in the Phase 1 paediatric studies (1.…”

“…A third of patients had peripheral sensory and/or motor neuropathy, but only rarely at grade 3 or higher. Other toxicities included haematological, fatigue, musculoskeletal weakness or pain, and nausea/vomiting (Berg et al, 2005;Kurtzberg et al, 2005;Cohen et al, 2008;DeAngelo, 2009).The combination of etoposide (VP) and cyclophosphamide (CPM) is used widely for refractory and relapsed lympho- (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain.…”

“…A third of patients had peripheral sensory and/or motor neuropathy, but only rarely at grade 3 or higher. Other toxicities included haematological, fatigue, musculoskeletal weakness or pain, and nausea/vomiting (Berg et al, 2005;Kurtzberg et al, 2005;Cohen et al, 2008;DeAngelo, 2009).…”

Irreversible neurological defects in the lower extremities after haploidentical stem cell transplantation: Possible association with nelarabine

“…These symptoms improved slowly after withdrawal. Berg et al reported a phase II study in which a total 151 of children and young adults received nelarabine for 5 consecutive days at daily doses of either 0.4, 0.6, 0.9, or 1.2 g/m 2 [18]. Thirty-one episodes of Grade 3 neurologic adverse events were observed in 27 patients (18% of patients).…”