y. Complete hematologic response (CHR) was observed in 78% of patients after 8 weeks of therapy. The complete cytogenetic response rate (CCyR) was 65%, comparable to the results observed in adults. Additionally, partial cytogenetic response (PCyR) was observed in 16%. The majority of patients who achieved a CCyR developed the CCyR between months 3 and 10 with a median time to response based on the Kaplan-Meier estimate of 6.74 months.
One open-label, single-arm study enrolled 14 pediatric patients with Ph+ chronic phase CML recurrent after stem cell transplant or resistant to interferon-alpha therapy. Patients ranged in age from 3-20 years old; 3 were 3-11 years old, 9 were 12-18 years old, and 2 were >18 years old. Patients were treated at doses of 260 mg/m2/day (n=3), 340 mg/m2/day (n=4), 440mg/m2/day (n=5) and 570 mg/m2/day (n=2). In the 13 patients for whom cytogenetic data are available, 4 achieved a major cytogenetic response, 7 achieved a complete cytogenetic response, and 2 had a minimal cytogenetic response.
In a second study, 2 of 3 patients with Ph+ chronic phase CML resistant to interferon-alpha therapy achieved a complete cytogenetic response at doses of 242 and 257 mg/m2/day.
14.3 Acute Lymphoblastic Leukemia
A total of 48Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients with relapsed/refractory disease were studied, 43 of whom received the recommended Gleevec dose of 600 mg/day.In addition 2 patients with relapsed/refractory Ph+ ALL received Gleevec 600 mg/day in a phase 1 study.
Confirmed and unconfirmedhematologic and cytogenetic response rates for the 43 relapsed/refractory Ph+ALL phase 2 study patients and for the 2 phase 1 patientsare shown in Table 16. The median duration of hematologic response was 3.4 months and the median duration of MCyR was 2.3 months.
Table 16 Effect of Gleevec on Relapsed/Refractory Ph+ ALL. Phase 2 Study (N=43) Phase 1 Study (N=2)
CHR 8 (19%) 2 (100%)
NEL 5 (12%)
RTC/PHR 11 (26%)
MCyR 15 (35%)
CCyR 9 (21%)
PCyR 6 (14%)
14.4 Myelodysplastic/Myeloproliferative Diseases
An open label, multicenter, phase 2 clinical trial was conducted testing Gleevec in diverse populations of patients suffering from life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases. This study included 7 patients with MDS/MPD. These patients were treated with Gleevec 400 mg daily. The ages of the enrolled patients ranged from 20 to 86 years.A further 24 patients with MDS/MPDaged 2 to 79 years were reported in 12 published case reports and a clinical study. These patients also received Gleevec at a dose of 400 mg daily with the exception of three patients who received lower doses. Of the total population of 31 patients treated for MDS/MPD, 14 (45%) achieved a completehematological response and 12 (39%) a major cytogenetic response (including 10 with a complete cytogenetic response). Sixteen patients had a translocation, involving chromosome 5q33 or 4q12, resulting in a PDGFR gene re-arrangement.All of these patients respondedhematologically (13 completely). Cytogenetic response was eva luated in 12 out of 14 patients, all of whom responded (10 patients completely). Only 1(7%) out of the 14patients without a translocation associated with PDGFR gene re-arrangement achieved a completehematological response and none achieved a major cytogenetic response.A further patient with a PDGFR gene re-arrangement i
