gh completion of therapy, and every 2 weeks for the first 2 months following therapy. In this study, asymptomatic positive PCR only for CMV was reported in 77/147 (52.4%) of MabCampath-treated patients; symptomatic CMV infection was reported less commonly in 23/147 MabCampath treated patients (16%). In the MabCampath arm 36/77 (46.8%) of patients with asymptomatic PCR positive CMV received antiviral therapy and 47/77 (61%) of these patients had MabCampath therapy interrupted. The presence of asymptomatic positive PCR for CMV or symptomatic PCR positive CMV infection during treatment with MabCampath had no measurable impact on progression free survival (PFS).
Previously treated B-CLL patients:
Determination of the efficacy of MabCampath is based on overall response and survival rates. Data available from three uncontrolled B-CLL studies are summarised in the following table:
Efficacy parameters
Study 1
Study 2
Study 3
Number of Patients
93
32
24
Diagnostic Group
B-CLL pts who had received an alkylating agent and had failed fludarabine
B-CLL pts who had failed to respond or relapsed following treatment with conventional chemotherapy
B-CLL (plus a PLL) pts who had failed to respond or relapsed following treatment with fludarabine
Median Age (years)
66
57
62
Disease Characteristics (%)
Rai Stage III/IV
B Symptoms
76
42
72
31
71
21
Prior Therapies (%):
Alkylating Agents
Fludarabine
100
100
100
34
92
100
Number of Prior Regimens (range)
3 (2-7)
3 (1-10)
3 (1-8)
Initial Dosing Regimen
Gradual escalation from 3 to 10 to 30 mg
Gradual escalation from 10 to 30 mg
Gradual escalation from 10 to 30 mg
Final Dosing Regimen
30 mg iv 3 x weekly
30 mg iv 3 x weekly
30 mg iv 3 x weekly
Overall Response Rate (%)
(95% Confidence Interval)
Complete Response
Partial Response
33
(23-43)
2
31
21
(8-33)
0
21
29
(11-47)
0
29
Median Duration of Response (months)
(95% Confidence Interval)
7
(5-8)
7
(5-23)
11
(6-19)
Median time to Response (months)
(95% Confidence Interval)
2
(1-2)
4
(1-5)
4
(2-4)
Progression-Free Survival (months)
(95% Confidence Interval)
4
(3-5)
5
(3-7)
7
(3-9)
Survival (months):
(95% Confidence Interval)
All patients
Responders
16 (12-22)
33 (26-NR)
26 (12-44)
44 (28-NR)
28 (7-33)
36 (19-NR)
NR = not reached
5.2 Pharmacokinetic properties
Pharmacokinetics were characterised in MabCampath-naive patients with B-cell chronic lymphocytic leukaemia (B-CLL) who had failed previous therapy with purine analogues. MabCampath was administered as a 2 hour intravenous infusion, at the recommended dosing schedule, starting at 3 mg and increasing to 30 mg, 3 times weekly, for up to 12 weeks. MabCampath pharmacokinetics followed a 2-compartment model and displayed non-linear elimination kinetics. After the last 30 mg dose, the median volume of distribution at steady-state was 0.15 l/kg (range: 0.1-0.4 l/kg), indicating that distribution was primarily to the extracellular fluid and plasma compartments. Systemic clearance decreased with repeated administration due to decreased receptor-mediated clearance (i.e. loss of CD52 receptors in the periphery). With repeated ad |
