For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.
Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.
A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death.
Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.
Excretion: Nelarabine and ara-G are partially eliminated by the kidneys.
* 197 +/- 189 L/h/m2 [Adult patients with refractory leukemia or lymphoma receiving doses of 199 to 2,900 mg/m2] * 259 +/- 409 L/h/m2 [Pediatric patients with refractory leukemia or lymphoma receiving doses of 104 to 2,900 mg/m2]