Clinical Trial Result Information

Title of Study:
An open-labeled, randomized, multicenter Phase III clinical trial of first-line treatment for patients with CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma with a standard CHOP chemotherapy regimen with or without rituximab (MabThera) (IDEC-C2B8).

Fast Facts:

Protocol number:	ML17429
Sponsor:	F. Hoffmann-La Roche Ltd
Company division:	Pharmaceutical
Product name:	MabThera/Rituxan
Generic name:	rituximab
Phase of development:	III
Therapeutic area, approved indication:	Non-Hodgkin's Lymphoma
Date of report:	2/8/2005

Clinical study summary:
This was an open-label, multicenter, randomized study of the efficacy and safety of MabThera plus a chemotherapy regimen compared with a chemotherapy regimen alone in patients with diffuse large B-cell non-Hodgkin’s lymphoma. Patients were randomized to receive either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus MabThera for 6 cycles.

Study center(s) :
9 centers in China.

Objectives:
Primary: To compare the response rate between patients treated with CHOP and those treated with CHOP plus MabThera. Secondary: To compare the safety profiles between the 2 treatment groups.

Methodology:
Patients randomized to the CHOP group received cyclophosphamide 750mg/m2, doxorubicin 50mg/m2 and vincristine 1.4mg/m2 intravenously on Day 1, and oral prednisone 100mg on Days 1-5; this treatment regimen was repeated every 3 weeks. Patients randomized to the MabThera + CHOP group received a slow intravenous infusion of MabThera 375mg/m2 once every 3 weeks, on Day 1 of each cycle. Except in the case of disease progression or withdrawal of consent, all patients were given 6 cycles of treatment.

Number of patients (planned/analyzed):
64 enrolled; 63 in the intent-to-treat population, and 63 in the statistical analysis.

Diagnosis and main criteria for inclusion:
To be eligible for inclusion, each patient was to fulfill each of the following criteria: CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma verified by histologic examination; 18–70 years of age; measurable and evaluable lymphoma lesions for assessment of efficacy; and ECOG performance status of 0–3.

Test product, dose and mode of administration or test procedure:
MabThera/iv/375 mg/m2 every 3 weeks + CHOP (see below).

Duration of treatment:
approximately 4.5 months.

Reference therapy, dose and mode of administration or reference procedure:
CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2, all by iv on Day 1; plus prednisone 100 mg/po/Days 1–5).

Criteria for evaluation (efficacy, safety):
Efficacy parameters: (1) Complete response; (2) Overall response; and (3) Disease progression. Safety parameters: (1) Adverse events; and (2) Serious adverse events.

Statistical methods:
The planned sample size was 60 patients. The intent-to-treat population consisted of all patients who took ≥1 dose of study medication. The safety population included all patients who received ≥1 dose of study medication and who had ≥1 safety follow-up, whether or not they withdrew from the study prematurely.

Summary (efficacy, safety, other results):
Of 63 patients analyzed, 16 patients (12 in CHOP group, 4 in CHOP plus MabThera group) withdrew from the study prematurely without completing 6 cycles of treatment, including 8 patients with disease progression, 4 with an adverse event, and 4 who withdrew consent. The rate of complete response in the CHOP plus MabThera group was similar to that in the CHOP group (42% vs 38%, P=0.7190). The overall response rate was 84% in the CHOP plus MabThera group compared with 66% in the CHOP group; however, the difference was not significant (P=0.0962). The addition of MabThera to CHOP chemotherapy significantly reduced treatment failure by reducing the rate of disease progression during the treatment period (3% vs 22%, P=0.0262).

Conclusions:
Addition of MabThera to the CHOP chemotherapy, given as first-line treatment for 6 cycles to patients with CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma, significantly reduced the treatment failure rate, without increasing clinical toxicity, compared with the CHOP regimen. An improvement in the response rate was not observed, possibly due to the small number of patients in this study.