Diffuse Large B-Cell LymphomaPhase 2NCT01040871
Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
A Phase 2 study testing VELCADE, Rituximab and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 1 site in Belgium.
Trial summary
This is a randomized, open-label, active-control, parallel-group, multicenter, multinational Phase 2 Study of the efficacy and safety of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- VELCADE, Rituximab and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 1 siteBelgium
- Study dates
- Jan 2010to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients 18 years or older.
- Newly Diagnosed non-GCB subtype of DLBCL (Stage II, III or IV).
- At least 1 measurable site of disease.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; and have a negative pregnancy test at screening.
- Male subjects must agree to use a double barrier method of birth control
Who cannot join
- Prior treatment with VELCADE.
- Prior extended radiotherapy or chemotherapy for lymphoma
- More than 150 mg/m2 of prior doxorubicin
- Major surgery within 3 weeks of study.
- Peripheral neuropathy or neuralgia of Grade 2 or worse.
- Active CNS lymphoma
Show all 14Show fewer
- Diagnosed or treated for a malignancy other than NHL, with some exceptions
- Pregnant or breast feeding
- Active systemic infection
- Documented of suspected human immunodeficiency virus (HIV)/AIDS
- Uncontrolled or severe cardiovascular disease
- Known allergies, hypersensitivity or intolerance to study drugs
- Serious medical condition that could interfere with study
- Concurrent treatment with another investigational agent
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Universitair Ziekenhuis Gent - UZ GENT, Hematologie, 9K12IE 9de verdiep- polikliniek Hematologie
Ghent
About this study
Official title: A Randomized, Open-Label, Multicenter Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
This is a randomized, open-label, active-control, parallel-group, multicenter, multinational Phase 2 Study of the efficacy and safety of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly Diagnosed Non-Germinal Center B-Cell (non-GCB) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL)
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VELCADEDrug
VELCADE intravenous on Days 1, 4, 8, and 11 of a 21 day (3 week) cycle for 6 cycles.
RituximabDrug
Rituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
CyclophosphamideDrug
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
DoxorubicinDrug
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
PrednisoneDrug
Orally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles
VincristineDrug
Intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| VR-CAP | Experimental | VR-CAP arm received rituximab 375 mg/m2 IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, VELCADE 1.3 mg/m2 IV on Days 1, 4, 8, and 11, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles. Receives: Drug: VELCADE; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone |
| R-CHOP | Active comparator | R-CHOP received rituximab 375 mg/m2IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, vincristine 1.4 mg/m2 (maximum total of 2 mg) IV on Day 1, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.Prednisone Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response (CR) Rate
Complete response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
- Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
- PET scan was negative.
- The spleen and/or liver, if enlarged before therapy on the basis of physical examination or CT scan, was not palpable on physical examination and was considered normal size by imaging studies; all splenic and hepatic nodules related to lymphomas disappeared.
- If bone marrow was involved before treatment, the infiltrate cleared on repeated bone marrow biopsy.
- No new sites of disease were detected.
Measured: 6 cycles
Secondary outcomes (7)
Overall Response Rate
Overall response = Complete Response (CR) + Partial Response (PR) Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Complete Response: see primary endpoint Partial Response: At least a 50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
Measured: 6 cycles
Rate of Durable Response
Proportion of subjects who achieved a CR or PR with duration of at least 6 months. Duration of response (CR or PR) was calculated from the date of initial documentation of a response to the date of first documented evidence of disease progression or death due to disease progression. Response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma.
Measured: Median follow up approx. 12 months
Rate of Durable Complete Response
Proportion of subjects who achieved a CR with duration of at least 6 months
Measured: Median follow up approx 12 months
Subsequent Anti-lymphoma Therapy Rate at 1-year
Kaplan-meier estimate of subsequent anti-lymphoma therapy at 1-year. Time to subsequent anti-lymphoma therapy was measured from the date of randomization to the start date of new treatment. Death due to disease progression prior to subsequent therapy was considered as an event. Otherwise, time to next anti-lymphoma treatment was censored at the date of death or the last date known to be alive.
Measured: 1 year
Progression-free Survival (PFS)Rate at 1-year
Kaplan-meier estimate of progression-free survival at 1-year. Progression-free survival was defined as the interval between the date of randomization and the date of first documented evidence of disease progression or death.
Measured: 1 year
Overall Survival Rate at 1-year
Kaplan-meier estimate of overall survival at 1-year measured from date of randomization.
Measured: 1 year
Change in Fatigue and Patient Utility Scores
Measured: 18-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2009 (estimated)
- Study startJan 2010
- Primary completionJun 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01040871
- Sponsor's protocol ID
- 26866138-LYM-2034
- Status last verified
- Dec 2013
- First submitted
- 29 Dec 2009
- Last updated
- 13 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. doi: 10.1182/blood-2015-03-632430. Epub 2015 Jul 31.
PubMed 26232170
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Multicenter Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT01040871
- Acronym / sponsor ID
- 26866138-LYM-2034
- Conditions
- Diffuse Large B-Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Study start
- Jan 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 30 Dec 2009 (estimated)
- Results
- Posted 27 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open-label, active-control, parallel-group, multicenter, multinational Phase 2 Study of the efficacy and safety of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Patients With Newly Diagnosed Non-Germinal Center B-Cell (non-GCB) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VR-CAP | Experimental | Drug: VELCADE, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: PrednisoneVR-CAP arm received rituximab 375 mg/m2 IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, VELCADE 1.3 mg/m2 IV on Days 1, 4, 8, and 11, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles. |
| R-CHOP | Active comparator | Drug: Rituximab, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: Prednisone, Drug: VincristineR-CHOP received rituximab 375 mg/m2IV on Day 1, cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, vincristine 1.4 mg/m2 (maximum total of 2 mg) IV on Day 1, and prednisone 100 mg/m2 orally on Days 1 through 5 of each 21-day (3-week) cycle for up to 6 cycles.Prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female patients 18 years or older.
- Newly Diagnosed non-GCB subtype of DLBCL (Stage II, III or IV).
- At least 1 measurable site of disease.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; and have a negative pregnancy test at screening.
Key exclusion criteria (14 listed)
- Prior treatment with VELCADE.
- Prior extended radiotherapy or chemotherapy for lymphoma
- More than 150 mg/m2 of prior doxorubicin
- Major surgery within 3 weeks of study.
- Peripheral neuropathy or neuralgia of Grade 2 or worse.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VELCADEVELCADE intravenous on Days 1, 4, 8, and 11 of a 21 day (3 week) cycle for 6 cycles. | Drug | VR-CAP |
| RituximabRituximab intravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles | Drug | R-CHOP, VR-CAP |
| CyclophosphamideIntravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles | Drug | R-CHOP, VR-CAP |
| DoxorubicinIntravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles | Drug | R-CHOP, VR-CAP |
| PrednisoneOrally on Day 1 to Day 5 of a 21 day (3 week) cycle for 6 cycles | Drug | R-CHOP, VR-CAP |
| VincristineIntravenous on Day 1 of a 21 day (3 week) cycle for 6 cycles | Drug | R-CHOP |
Primary outcome
Complete Response (CR) Rate
Time frame: 6 cycles
Complete response was evaluated by an Independent Radiology Review Committee using available computed tomography (CT) and positron emission tomography (PET) scans collected at Baseline, end of cycle 3, and end of cycle 6 (or end of treatment) based on the Revised Response Criteria for Malignant Lymphoma. 1. Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. PET scan was negative. 3. The spleen and/or liver, if enlarged before therapy on the basis of physical examination or CT scan, was not palpable on physical examination and was considered normal size by imaging studies; all splenic and hepatic nodules related to lymphomas disappeared. 4. If bone marrow was involved before treatment, the infiltrate cleared on repeated bone marrow biopsy. 5. No new sites of disease were detected.
7 secondary outcomes
Overall Response Rate
Time frame: 6 cycles
Rate of Durable Response
Time frame: Median follow up approx. 12 months
Rate of Durable Complete Response
Time frame: Median follow up approx 12 months
Subsequent Anti-lymphoma Therapy Rate at 1-year
Time frame: 1 year
Progression-free Survival (PFS)Rate at 1-year
Time frame: 1 year
Overall Survival Rate at 1-year
Time frame: 1 year
Change in Fatigue and Patient Utility Scores
Time frame: 18-24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26232170Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. doi: 10.1182/blood-2015-03-632430. Epub 2015 Jul 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VELCADE, Rituximab and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response (CR) Rate (time frame: 6 cycles). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01040871, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2014.