ABBREVIATED CLINICAL STUDY REPORT

ABBREVIATED CLINICAL STUDY REPORT
TITLE:
LONG-TERM FOLLOW-UP STUDY FOR M 39023:
M 39023 FOLLOW-UP
PROTOCOL NUMBER:
Version 1.9 (18 September 2007)
EudraCT Number:
Not applicable
STUDY DRUG:
Not applicable
INDICATION:
CD20-positive follicular lymphoma
REPORT NUMBER:
CSR ML21100
IND:
Not applicable
PHASE:
Non-interventional observational trial
SPONSOR:
Roche Pharma AG
Emil-Barell-Straße 1
D-79639 Grenzach-Wyhlen
SPONSOR’S
MEDICAL OFFICER:
Kerstin Kellershohn, Ph.D.
NAME OF PRINCIPAL
INVESTIGATOR:
Prof Michael Herold, MD
HELIOS Klinikum Erfurt GmbH
D-99089 Erfurt
REPORT PREPARED BY:
Andreas Straka, PhD
Ecron Acunova GmbH
D-60528 Frankfurt
RECORDS RETENTION:
F Hoffmann-La Roche Central Records
STUDY DATES:
Initiation:
September 2007
Completion: June 2013
CONFIDENTIAL
Abbreviated Clinical Study Report: IDEC C2B8/Rituximab
Roche Clinical Study Report ML21100 - Version 1.0; 03 February 2014
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REPORT DATE:
03 February 2014
PERSONNEL RESPONSIBLE
FOR CLINICAL AND
STATISTICAL ANALYSES:
Ernst Blümner, MSc Math, MD
Ecron Acunova GmbH
D-60528 Frankfurt
GCP COMPLIANCE: This study was conducted in accordance with GCP guidelines.
CONFIDENTIAL
Abbreviated Clinical Study Report: IDEC C2B8/Rituximab
Roche Clinical Study Report ML21100 - Version 1.0; 03 February 2014
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Study Design
Title of Study: Long-term Follow-up study for M 39023: M 39023 Follow-up
Phase of Development: Non-interventional observational trial
Study Period: September 2007 to June 2013
Investigators / Centers and Countries: Coordinating Investigator according to German Drug Law
(Leiter der klinischen Prüfung (LKP)): Prof Michael Herold, MD, Erfurt, Germany. For a complete
list of all participating investigators please refer to Appendix 8.1.4.
The follow-up study was performed in a total of 34 centers in Germany.
Publication (Reference): None
Objectives
Primary:
 To record overall survival of patients with CD20-positive follicular lymphoma (FL)
Secondary:
 To examine product-specific efficacy
Number of Subjects:
Planned: Up to 200 (depending on patients having finished the M 39023 trial)
The present study ML21100 encompasses 129 patients with follicular lymphoma (Rituximab +
MCP: 77, MCP: 52) who were followed-up further 5 years after having finished the preceding
M 39023 trial and its 4-year follow-up.
Analyzed: The data of these patients were analysed together with the data of the preceding
study M 39023, i.e. of a total of 201 patients with follicular lymphoma (ITTcbcc/FL population).
Diagnosis and Main Criteria:
For Inclusion: Patients with follicular lymphoma that have been treated within the M 39023 trial
Trial and Reference Drug: None. This non-interventional trial was a prolongation of study
M 39023, referring to the treatment groups of this study.
Dose / Route / Regimen / Duration: Not applicable
Criteria for Evaluation:

Efficacy:
Primary parameter(s): Overall survival (OS), progression-free survival (PFS)
Secondary parameters: Interferon (IFN) maintenance therapy, duration of IFN therapy,
observation time, event-free survival (EFS), disease-free survival (DFS), response duration,
time to next treatment, cause-specific death

Safety:
According to the observational plan, only serious adverse events that were assessed by the
investigators as caused by drug therapy and Roche products were to be documented in this
follow-up study. It was in the responsibility of the investigators to report these events
directly to the Medical Affairs Unit of Roche Pharma AG.
CONFIDENTIAL
Abbreviated Clinical Study Report: IDEC C2B8/Rituximab
Roche Clinical Study Report ML21100 - Version 1.0; 03 February 2014
3 of 5
Statistical Methods:
Primary parameter(s): The time to event data overall survival and progression-free survival were
compared by means of Kaplan-Meier estimators and log-rank tests at the significance level of
alpha = 5 % for difference between the two treatment groups Rituximab + MCP vs. MCP.
Censoring: For overall survival the censoring date was the last observation time.
One-hundred and twenty-nine (129) patients with follicular lymphoma were documented in the
present study ML21100 over 5 years. The data was combined with that of the preceding study
M 39023 and its 4-year follow-up. The assignments to the treatment groups and the analysis
populations were maintained. Thus, the analyses were conducted on a total of 201 patients in
the ITTcbcc/FL population.
Although not mentioned in the observational plan, analyses were additionally performed on the
ITT, ITTlpic and ITTcc(mcl) populations (consisting of 358, 34 and 90 patients, respectively).
For the ITTcbcc/FL and ITT populations the analyses were also conducted by IFN maintenance
therapy (yes/no).
In this report, only the results of the analyses regarding the ITTcbcc/FL population, mentioned as
ITT FL population, are described.
Secondary parameters: The secondary efficacy parameters were analyzed using descriptive
statistics. The time to event data event-free survival, disease-free survival, response duration,
and time to next treatment were compared by means of Kaplan-Meier estimators and log-rank
tests at the significance level of alpha = 5 % for difference between the treatment groups.
Additionally for event-free survival the analyses were conducted by IFN maintenance therapy
(yes/no).
Censoring: For time to progression, event-free survival, duration of response, and disease-free
survival the censoring date was the last response assessment date. For time to next treatment
the censoring date was the last time point when it was confirmed the patient did not start a new
treatment.
Cause-specific death was evaluated using Fisher’s two-sided exact test at the significance level
of alpha = 5 % for difference between the treatment groups.
All tests were exploratory.
Methodology:
As this was a non-interventional trial, physicians’ decision concerning therapy, diagnostic
procedures and frequency of medical examination was not influenced with the implementation of
this study.
No study-specific procedures were requested. Treatment and diagnosis occurred only according
to clinical practice.
Details of the study can be found in the observational plan (see Appendix 8.1.1).
Results:
In this report, only the results of the analyses regarding the ITTcbcc/FL population, mentioned as
ITT FL population, are described.
The analysis of the time to event data after completion of the additional 5-year follow-up phase
yielded results which were in favor of Rituximab + MCP for all evaluated parameters in the
ITT FL population (p values < 0.05, exploratory).
After randomization to the M 39023 trial cause-specific deaths, i.e. deaths related to NHL, were
observed for 9.5% of patients treated with Rituximab + MCP and for 21.9% of patients treated
with MCP (ITT FL population). This difference between the treatments was medically relevant in
favor of Rituximab + MCP (p = 0.0189).
Subanalyses of patients who received an IFN maintenance therapy or not did also show superior
results for Rituximab + MCP vs. MCP, indicating that there is no distinct bias to the time to event
data in the follow-up phase.
CONFIDENTIAL
Abbreviated Clinical Study Report: IDEC C2B8/Rituximab
Roche Clinical Study Report ML21100 - Version 1.0; 03 February 2014
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Discussion and Conclusions:
Overall, the results of the analysis of the time to event data after completion of the additional
5-year follow-up phase in study ML21100 confirm the results of the analysis encompassing the
data after the end of therapy and the 4-year follow-up phase in study M 39023 and show that
those effects are maintained.
The results are very promising and indicate that combined treatment with Rituximab and MCP
chemotherapy may improve the outcome of patients with follicular lymphoma of advanced
stages also over a long period of time.
Date of the Report:
03 February 2014
CONFIDENTIAL
Abbreviated Clinical Study Report: IDEC C2B8/Rituximab
Roche Clinical Study Report ML21100 - Version 1.0; 03 February 2014
5 of 5

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