cute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) that had relapsed following or was refractory to at least two prior induction regimens. ARRANON 1,500 mg/m2 was administered intravenously over 2 hours on days 1, 3 and 5 repeated every 21 days. Patients who experienced signs or symptoms of grade 2 or greater neurologic toxicity on therapy were to be discontinued from further therapy with ARRANON. Seventeen patients had a diagnosis of T-ALL and 11 had a diagnosis of T-LBL. For patients with ≥2 prior inductions, the age range was 16-65 years (mean 34 years) and most patients were male (82%) and Caucasian (61%). Patients with central nervous system (CNS) disease were not eligible.
Complete response (CR) in this study was defined as bone marrow blast counts ≤5%, no other evidence of disease, and full recovery of peripheral blood counts. Complete response without complete hematologic recovery (CR*) was also assessed. The results of the study for patients who had received ≥2 prior inductions are shown in Table 3.
Table 3. Efficacy Results in Adult Patients With ≥2 Prior Inductions Treated with 1,500 mg/m2 of ARRANON Administered Intravenously Over 2 Hours on Days 1, 3, and 5 Repeated Every 21 Days
|
|
N = 28
|
|
CR plus CR* % (n) [95% CI]
|
21% (6) [8%, 41%]
|
|
CR % (n) [95% CI]
|
18% (5) [6%, 37%]
|
|
CR* % (n) [95% CI]
|
4% (1) [0%, 18%]
|
|
Duration of CR plus CR* (range in weeks)1
|
4 to 195+
|
|
Median overall survival (weeks) [95% CI]
|
20.6 weeks [10.4, 36.4]
|
CR = Complete response
CR* = Complete response without hematologic recovery
1 Does not include 1 patient who was transplanted (duration of response was 156+ weeks).
The mean number of days on therapy was 56 days (range of 10 to 136 days). Time to CR plus CR* ranged from 2.9 to 11.7 weeks.
INDICATIONS AND USAGE
ARRANON is indicated for the treatment of 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. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.
CONTRAINDICATIONS
ARRANON is contraindicated in patients who have a history of hypersensitivity to nelarabine or any other components of ARRANON.
WARNINGS
ARRANON should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.
Neurologic Events (see boxed WARNING)
ARRANON is a potent antineoplastic agent with potentially significant toxic side effects. Neurotoxicity is the dose-limiting toxicity of nelarabine. Patients undergoing therapy with ARRANON should be closely observed for signs and symptoms of neurologic toxicity.
Common signs and symptoms of nelarabine-related neurotoxicity include somnolence, confusion, convulsions, ataxia, paresthesias, and hypoesthesia. Severe neurologic toxici
