Approved October 2005
Cancer & Oncology
Arranon (nelarabine) is a cytotoxic deoxyguanosine analogue prodrug. The drug disrupts DNA synthesis in rapidly dividing cells, inducing cellular apoptosis. Additional mechanisms of cytotoxic activity may also exist.
Arranon is specifically indicated for the treatment of pediatric and adult patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.
Arranon is supplied as a clear, colorless, sterile solution designed for intravenous infusion. Recommended adult dosage is 1,500 mg/m2 delivered as a 2 hour infusion on days 1, 3, and 5 of a 21 day treatment cycle. Recommended pediatric dosage is 650 mg/m2 delivered as a 1 hour infusion daily for days 1 through 5 of a 21 day treatment cycle. Treatment cycles should be repeated until evidence of disease progression is observed.
Approval of Arranon was supported by a pair of clinical trials, investigating the drug in both pediatric and adult patients.
Arranon was investigated in a phase II trial of pediatric patients age 21 years and younger. This single-arm, multi-center enrolled 84 patients with refractory T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL); 31 of these subjects had received one prior chemotherapy regimen, and 39 had received two or more. All patients received 650 mg/m2 via one hour infusion for 5 consecutive days in 21 day treatment cycles. Results indicated that 13% of subjects (n=5) achieved complete disease response (bone marrow blast counts<5%) and full recovery of peripheral blood counts, and 10% (n=4) achieved complete disease response without full hematological recovery. Response duration was 3.3 to 9.3 weeks, and median overall survival was 13.1 weeks.
The drug's safety and efficacy in adult patients was investigated was investigated in an additional phase II study. This single-arm, multi-center study enrolled 39 T-ALL and T-LBL patients, 28 of whom had received at least two courses of chemotherapy. Among these subjects, 18% (n=5) achieved complete response and hematological recovery, and 4% (n=1). Duration of complete response was 4 to 195+ weeks, and median overall survival was 20.6 weeks.
Ongoing Study Commitments
Adverse events associated with the use of Arranon may include, but are not limited to, the following:
In addition, neurological adverse events were observed in 64% of subjects. Most were mild to moderate (grade 1-2), including headache, somnolence, neuropathy, hypoesthesia. Grade 4 and grade 5 (fatal) adverse neurological events were also obsered, including 3rd and 6th nerve paralysis, progressive multifocal leukoencephalopathy, demyelination similar to Guillain-Barré syndrome, cerebral and intracranial hemorrhage, coma, and metabolic encephalopathy. Close monitoring of such events is recommended, and appearance of moderate (grade 2) or higher neurological toxicities may require discontinuation of treatment.
Arranon is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). The drug is ultimately metabolized into the active 5'-triphosphate ara-GTP, which disrupts DNA synthesis and induces apoptosis. Additional cytotoxic activities may exist, but these are not fully understood.
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