ells or progenitor cells.
First line B-CLL patients
The safety and efficacy of MabCampath were eva luated in a Phase 3, open-label, randomized comparative trial of first line (previously untreated) Rai stage I-IV B-CLL patients requiring therapy (Study 4). MabCampath was shown to be superior to chlorambucil as measured by the primary endpoint progression free survival (PFS) (see Figure 1).
Figure 1: Progression free survival in first line study (by treatment group)
The secondary objectives included complete response (CR) and overall response (CR or partial response) rates using the 1996 NCIWG criteria, the duration of response, time to alternative treatment and safety of the two treatment arms.
Summary of first-line patient population and outcomes
Independent review of response rate and duration
MabCampath
n=149
Chlorambucil
n=148
P value
Median Age (Years)
59
60
Not Applicable
Rai Stage III/IV Disease
33.6%
33.1%
Not Applicable
Overall Response Rate
83.2%
55.4%
<0.0001*
Complete Response
24.2%
2.0%
<0.0001*
MRD negative****
7.4%
0.0%
0.0008*
Partial Response
59.1%
53.4%
Not Applicable
Duration of Response**, CR or PR (Months)
K-M median (95% Confidence Interval)
N=124
16.2
(11.5, 23.0)
N=82
12.7
(10.2, 14.3)
Not Applicable
Time to Alternative Treatment (Months)
K-M median (95% Confidence Interval)
23.3
(20.7, 31.0)
14.7
(12.6, 16.8)
0.0001***
*Pearson chi-square test or Exact test
** Duration of best response
*** log-rank test stratified by Rai group (Stage I-II vs III-IV)
**** by 4-colour flow
Cytogenetic Analyses in first line B-CLL patients:
The cytogenetic profile of B-CLL has been increasingly recognized as providing important prognostic information and may predict response to certain therapies. Of the first-line patients (n=282) in whom baseline cytogenetic (FISH) data were available in Study 4, chromosomal aberrations were detected in 82%, while normal karyotype was detected in 18%. Chromosomal aberrations were categorized according to Döhner's hierarchical model. In first line patients, treated with either MabCampath or chlorambucil, there were 21 patients with the 17p deletion, 54 patients with 11q deletion, 34 patients with trisomy 12, 51 patients with normal karyotype and 67 patients with sole 13q deletion.
ORR was superior in patients with any 11q deletion (87% v 29%; p<0.0001) or sole deletion 13q (91% v 62%; p=0.0087) treated with MabCampath compared to chlorambucil. A trend toward improved ORR was observed in patients with 17p deletion treated with MabCampath (64% v 20%; p=0.0805). Complete remissions were also superior in patients with sole 13q deletion treated with MabCampath (27% v 0%; p=0.0009). Median PFS was superior in patients with sole 13q deletion treated with MabCampath (24.4 v 13.0 months; p=0.0170 stratified by Rai Stage). A trend towards improved PFS was observed in patients with 17p deletion, trisomy 12 and normal karyotype, which did not reach significance due to small sample size.
Assessment of CMV by PCR:
In the randomized controlled trial in first line patients (Study 4), patients in the MabCampath arm were tested weekly for CMV using a PCR (polymerase chain reaction) assay from initiation throu |
