o;s Oncology Group (COG P9673). This study included patients 21 years of age and younger, who had relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL). Eighty-four (84) patients, 39 of whom had received two or more prior induction regimens, were treated with 650 mg/m2/day of ARRANON administered intravenously over 1 hour daily for 5 consecutive days repeated every 21 days (see Table 1). Patients who experienced signs or symptoms of grade 2 or greater neurologic toxicity on therapy were to be discontinued from further therapy with ARRANON.
Table 1. Pediatric Clinical Study - Patient Allocation
|
Patient Population
|
N
|
|
Patients treated at 650 mg/m2/day x 5 days every 21 days.
|
84
|
|
Patients with T-ALL or T-LBL with two or more prior induction treated at 650 mg/m2/day x 5 days every 21 days.
|
39
|
|
Patients with T-ALL or T-LBL with one prior induction treated at 650 mg/m2/day x 5 days every 21 days.
|
31
|
The 84 patients ranged in age from 2.5-21.7 years (overall mean, 11.9 years), 52% were 3 to 12 years of age and most were male (74%) and Caucasian (62%). The majority (77%) of patients had a diagnosis of T-ALL.
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 full hematologic recovery (CR*) was also assessed as a meaningful outcome in this heavily pretreated population. Duration of response is reported from date of response to date of relapse, and may include subsequent stem cell transplant. Efficacy results are presented in Table 2.
Table 2. Efficacy Results in Patients 21 Years of Age and Younger at Diagnosis With ≥2 Prior Inductions Treated with 650 mg/m2 of ARRANON Administered Intravenously Over 1 Hour Daily for 5 Consecutive Days Repeated Every 21 Days
|
|
N = 39
|
|
CR plus CR* % (n) [95% CI]
|
23% (9) [11%, 39%]
|
|
CR % (n) [95% CI]
|
13% (5) [4%, 27%]
|
|
CR* % (n) [95% CI]
|
10% (4) [3%, 24%]
|
|
Duration of CR plus CR* (range in weeks)1
|
3.3 to 9.3
|
|
Median overall survival (weeks) [95% CI]
|
13.1 [8.7, 17.4]
|
CR = Complete response
CR* = Complete response without hematologic recovery
1 Does not include 5 patients who were transplanted or had subsequent systemic chemotherapy (duration of response in these 5 patients was 4.7 to 42.1 weeks).
The mean number of days on therapy was 46 days (range of 7 to 129 days). Median time to CR plus CR* was 3.4 weeks (95% CI: 3.0, 3.7).
Adult Clinical Study
The safety and efficacy of ARRANON in adult patients were studied in a clinical trial conducted by the Cancer and Leukemia Group B (CALGB). This study included 39 treated patients, 28 who had T-cell a
