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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00486759




Registration number
NCT00486759
Ethics application status
Date submitted
14/06/2007
Date registered
15/06/2007
Date last updated
25/07/2017

Titles & IDs
Public title
A Study of Bevacizumab (Avastin) in Combination With Rituximab (MabThera) and CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], Prednisone) Chemotherapy in Patients With Diffuse Large B-cell Lymphoma
Scientific title
A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Trial Comparing the Efficacy of Bevacizumab in Combination With Rituximab and CHOP (R-CHOP + Bevacizumab) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With CD20-positive Diffuse Large B-cell Lymphoma (DLBCL)
Secondary ID [1] 0 0
BO20603
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Rituximab
Treatment: Drugs - CHOP
Treatment: Drugs - Placebo

Experimental: Bevacizumab + rituximab + CHOP - Patients received bevacizumab 5 mg/kg/week on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).

Active comparator: Placebo + rituximab + CHOP - Patients received placebo to bevacizumab on Day 1 of each cycle + rituximab 375 mg/m\^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone).


Treatment: Drugs: Bevacizumab
Bevacizumab was administered at a dose of 15 mg/kg IV on Day 1 of each 21-day cycle for 8 cycles or at a dose 10 mg/kg IV on Day 1 of each 14-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.

Treatment: Drugs: Rituximab
Rituximab was administered at a dose of 375 mg/m\^2 IV on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.

Treatment: Drugs: CHOP
Cyclophosphamide was administered at a dose of 750 mg/m\^2 IV on Day 1 of each cycle. Doxorubicin was administered at a dose of 50 mg/m\^2 IV on Day 1 of each cycle. Vincristine was administered at a dose of 1.4 mg/m\^2 IV (maximum of 2 mg) on Day 1 of each cycle. Prednisone was administered at a dose of 100 mg orally on Days 1-5 of each cycle. All 4 drugs were administered either every 21 days for 8 cycles or every 14 days for 6 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.

Treatment: Drugs: Placebo
Placebo to bevacizumab was administered on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Baseline to end of the study (up to 4 years, 4 months)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Baseline to end of the study (up to 4 years, 4 months)
Secondary outcome [2] 0 0
Overall Response (OR) Assessed According to the Revised Response Criteria for Malignant Lymphoma
Timepoint [2] 0 0
At the end of treatment (Cycle 8, up to 12 months)

Eligibility
Key inclusion criteria
* Adult patients, = 18 and < 80 years of age.
* CD20-positive diffuse large B-cell lymphoma.
* Low-intermediate, high-intermediate, or high risk disease and/or bulky tumor (largest diameter = 7.5 cm).
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment for diffuse large B-cell lymphoma.
* Types of non-Hodgkin's lymphoma other than diffuse large B-cell lymphoma (DLBCL).
* Central nervous system (CNS) involvement of lymphoma.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/07/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2011
Sample size
Target
Accrual to date
Final
787
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Greenslopes Private Hospital; Gallipoli Research Centre - Greenslopes
Recruitment hospital [2] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [3] 0 0
Royal Adelaide Hospital; Haematology, Institute of Medical Veterinary Science - Adelaide
Recruitment hospital [4] 0 0
Ashford Cancer Center Research - Kurralta Park
Recruitment hospital [5] 0 0
Frankston Hospital; Oncology/Haematology - Frankston
Recruitment hospital [6] 0 0
Peter Maccallum Cancer Institute; Medical Oncology - Melbourne
Recruitment hospital [7] 0 0
Alfred Hospital; Bone Marrow Transplant Unit - Melbourne
Recruitment hospital [8] 0 0
Border Medical Oncology; Murray Valley Private Hospital - Wodonga
Recruitment hospital [9] 0 0
Fremantle Hospital; Haematology - Fremantle
Recruitment postcode(s) [1] 0 0
4120 - Greenslopes
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
3181 - Melbourne
Recruitment postcode(s) [8] 0 0
3690 - Wodonga
Recruitment postcode(s) [9] 0 0
6160 - Fremantle
Recruitment outside Australia
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United States of America
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Graz
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Wien
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GO
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Chiang Mai
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Thailand
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Khon Kaen
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United Kingdom
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Birmingham
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Bradford
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Hampshire
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Harlow
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Leicester
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Liverpool
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London
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Middx
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Oxford
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Sheffield
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This 2-arm study was designed to compare the efficacy and safety of bevacizumab (Avastin) in combination with rituximab (MabThera) and CHOP (cyclophosphamide, hydroxydaunorubicin \[doxorubicin\], Oncovin \[vincristine\], prednisone) chemotherapy (R-CHOP) versus rituximab plus CHOP chemotherapy (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL). Patients were randomized to receive 8 cycles of treatment with R-CHOP plus bevacizumab or R-CHOP plus placebo. Treatment with bevacizumab/placebo and R-CHOP was given either on a 2-week or 3-week schedule and bevacizumab was given at a weekly average dose of 5 mg/kg (10 mg/kg for 2-week cycles and 15 mg/kg for 3-week cycles).
Trial website
https://clinicaltrials.gov/study/NCT00486759
Trial related presentations / publications
McCord R, Bolen CR, Koeppen H, Kadel EE 3rd, Oestergaard MZ, Nielsen T, Sehn LH, Venstrom JM. PD-L1 and tumor-associated macrophages in de novo DLBCL. Blood Adv. 2019 Feb 26;3(4):531-540. doi: 10.1182/bloodadvances.2018020602.
Seymour JF, Pfreundschuh M, Trneny M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. doi: 10.3324/haematol.2013.100818. Epub 2014 Jun 3.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00486759