Summary
EudraCT Number:2006-005520-16
Sponsor's Protocol Code Number:BO20603
National Competent Authority:Czech Republic - SUKL
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2007-05-14
Trial results View results
A. Protocol Information
A.1Member State ConcernedCzech Republic - SUKL
A.2EudraCT number2006-005520-16
A.3Full title of the trial
A multi-center, randomized, double-blind, placebo-controlled phase III trial comparing the efficacy of bevacizumab in combination with rituximab and CHOP (RA-CHOP) versus rituximab and CHOP (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL)
A.3.2Name or abbreviated title of the trial where available
MAIN
A.4.1Sponsor's protocol code numberBO20603
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorF. Hoffmann-La Roche Ltd
B.1.3.4CountrySwitzerland
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Avastin
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameAvastin
D.3.2Product code RO4876646
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNbevacizumab
D.3.9.1CAS number 216974-75-3
D.3.9.2Current sponsor codeRO4876646
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Yes
D.3.11.13.1Other medicinal product typeRecombinant humanised monoclonal antibody
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
D.8.4Route of administration of the placeboIntravenous use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Previously untreated CD20-positive Diffuse Large B-Cell Lymphoma (DLBCL) patients who have low-intermediate, high-intermediate, or high-risk disease according to the IPI score and patients with bulky tumor (largest diameter > 7.5 cm) regardless of disease risk according to the IPI.
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 8.1
E.1.2Level LLT
E.1.2Classification code 10012818
E.1.2Term Diffuse large B-cell lymphoma
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To follow–up safety in previously untreated patients with diffuse large B cell lymphoma (DLBCL) with at least low-intermediate risk disease according to the IPI or bulky disease regardless of IPI risk category who were enrolled into the BO20603 study and treated with rituximab and CHOP (R-CHOP) alone versus patients treated with any cycle of bevacizumab in combination with rituximab and CHOP (RA-CHOP).
E.2.2Secondary objectives of the trial
Secondary objectives: not applicable

Exploratory objectives:
• To identify prognostic biomarkers for response to treatment
• To identify predictive biomarkers for safety
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
• Patients previously randomized to the BO20603 study (MAIN) and who have received any cycle of study treatment prior to termination of bevacizumab treatment by 31 May 2010.

• Previously randomized patients providing written informed consent to continue study participiation according to this modified version of the study protocol (version D).
E.4Principal exclusion criteria
• Patients not randomized to the BO20603 study prior to 01 June 2010 following the DSMB recommendation which became effective on 31 May 2010.

• Previously randomized patients who are not willing to sign the amended informed consent.
E.5 End points
E.5.1Primary end point(s)
To follow-up safety in patients treated with R-CHOP versus patients treated with any cycle of bevacizumab in combination with rituximab and CHOP (RA-CHOP) in previously untreated patients with diffuse large B cell lymphoma (DLBCL) with at least low-intermediate risk disease according to the IPI or bulky disease regardless of IPI risk category.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy No
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Follow-up and Biomarker analysis
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned5
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA30
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The End of the study is defined as the date of the last follow-up visit (12 months
after last R-CHOP treatment cycle during the induction treatment phase) of the last
patient randomized. Study end might occur earlier if all patients have progressed, died or withdrawn from the study.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months6
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) Yes
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women Yes
F.3.3.4Nursing women Yes
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state40
F.4.2 For a multinational trial
F.4.2.1In the EEA 365
F.4.2.2In the whole clinical trial 787
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
All patients will continue until the last patient randomized has completed the 12-month follow-up period after having received the last treatment cycle (R-CHOP). All patients except those who were withdrawn because of progressive disease, will have follow-up clinical visits:
• Every 3 months (±7 days) until 24 month, or disease progression, or until study end, whichever occurs first;
• Thereafter every 6 months (±14 days), until disease progression, or until study
end, whichever occurs first.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2007-06-18
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2007-08-08
P. End of Trial
P.End of Trial StatusOngoing