Clinical Trial Result Information

Protocol number
M39052

Title of Study
An open, uncontrolled, monocentric clinical trial to evaluate activity and toxicity of rituximab in chronic lymphocytic leukemia (CLL) patients responsive to first line therapy with chlorambucil (CB) and prednisone (PDN).

Sponsor
F Hoffmann-La Roche Ltd

Company division
Pharmaceutical

Product name
MabThera/Rituxan

Generic name
rituximab

Therapeutic area
Lymphocytic Leukemia, Chronic

Clinical study summary
This was an open-label, uncontrolled, mono-center study of CLL patients who have achieved complete or partial clinical response after a regimen of chlorambucil and prednisone, receiving MabThera (rituximab) to achieve or maintain complete clinical response and to obtain and maintain biological response.

Study center(s)
1 center in Italy.

Phase of development
II

Objectives
Primary: To evaluate the activity of MabThera in terms of rate of clinical and biological (immunological and molecular) response at 1 month after the end of treatment.
Secondary: To evaluate the activity of MabThera in terms of: clinical and biological disease free-survival (3 years follow-up); event-free survival; overall survival. To evaluate the toxicity of MabThera.

Methodology
Patients were enrolled in a single treatment group, to receive 4 weekly doses (375mg/m²) of MabThera. The clinical and biological response was evaluated 1 month after the end of treatment. The duration of response was evaluated in a follow-up period of 3 years.

Number of patients (planned/analyzed)
20 enrolled. 19 patients evaluated for efficacy and safety.

Diagnosis and main criteria for inclusion
Adult patients, affected by B-CLL, age >60 years, with signs of activity according to NCI criteria and in complete or partial response following 6 courses of chlorambucil and prednisone.

Test product, dose and mode of administration or test procedure
MabThera (rituximab) 375mg/m², was administered intravenously at weekly intervals.

Duration of treatment
4 weeks.

Reference therapy, dose and mode of administration or reference procedure
N/A.

Criteria for evaluation (efficacy, safety)
Primary: Rate of clinical response according to NCI criteria, evaluated 1 month after end of treatment. Rate of biological response (including immunological and molecular response rates) evaluated 1 month after end of treatment.
Secondary: Clinical disease-free survival, biological disease-free survival, event-free survival, overall survival.

Safety: Common Toxicity Criteria (CTC) toxicity grading system; clinical adverse events including all other AEs not covered by the CTC toxicity grading system; infections; laboratory parameters.

Statistical methods
No statistical hypothesis testing was planned. Descriptive summary statistics were used. Continuous variables were summarized by descriptive statistics (number, mean, standard deviation, median, minimum and maximum). Categorical variables were summarized using number and percentages.

Two analysis populations were used for the primary efficacy parameters:

• intent to treat analysis population: all patients who had received at least one infusion of MabThera
• per protocol analysis population: all patients who had received the complete treatment with MabThera and had not incurred any major protocol violations

For the primary endpoint:

• Clinical response: complete and partial response at 1 month after the end of treatment
• Biological response:
  • immunological response: complete and partial immunological response at 1 month after the end of treatment
  • molecular response: the absence of the rearrangements of region of chromosome coding the Ig heavy chains by PCR analysis. If this parameter was positive, when evaluated 1 month after the end of treatment, remission was not reached.

For the secondary endpoints:

• Clinical disease-free survival, biological disease-free survival, event-free survival, overall survival

Summary (efficacy, safety, other results)
Efficacy: At the end of treatment, a documented complete clinical response was achieved in 13 patients (68.4%) and partial clinical response was maintained in 6 patients (31.6%). In all but 2 cases, no enlarged nodes or splenomagaly were observed.
A total of 16 patients were evaluated for immunological response. A complete or partial immunological response was present in 13 patients (68.4%).  Two out of seventeen patients were found to have a molecular response.
The median follow-up time was 37.5 months (36.5-44.4); only 1 patient did not experience clinical progression during 3 years of follow-up. The median clinical progression-free survival after achievement of response was 16.3 months, whereas the median immunological/clinical progression-free survival was 5 months. Event-free survival had a median duration of 18.2 months, and only one patient died during the 3 year follow-up.

Safety: Mild infusion-related side effects were observed in 3 cases. No patient showed hematologic toxicity or infection. No serious adverse events were reported. One patient died during the follow-up, due to lung cancer. No marked laboratory abnormalities were detected.

Conclusions
The results of this study indicate that MabThera, given as post-remission therapy in older CLL patients treated with chlorambucil and prednisolone, produced a clinical benefit with a good safety profile in the majority of cases.

Publications (references, if available)
Haematologica 2007; Vol 92 (s1), Abstract 0124

Date of report
5/2/2007

Click here for the protocol registry listing of this trial.