LymphomaPhase 2NCT00428142
Bortezomib, Combination Chemotherapy, and Rituximab as First-Line Therapy in Treating Patients With Stage III or Stage IV Follicular Non-Hodgkin's Lymphoma
A Phase 2 study testing rituximab, bortezomib and cyclophosphamide in people with Lymphoma, run by NCIC Clinical Trials Group at 19 sites in Canada.
Trial summary
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- rituximab, bortezomib and cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 19 sitesCanada
- Study dates
- 1 May 2007to 6 Jan 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed follicular non-Hodgkin's lymphoma meeting the following criteria:
- Stage III or IV disease
- Grade 1, 2, or 3 disease requiring systemic first-line treatment
- No transformation to diffuse large cell lymphoma
- At least 1 bidimensionally measurable lesion meeting 1 of the following criteria:
- Lymph nodes > 1.5 cm x 1.0 cm by physical exam or CT scan
- Other non-nodal lesion ≥ 1.0 cm x 1.0 cm by MRI or CT scan OR ≥ 1.0 cm x 1.0 cm (e.g., skin lesions or nodules) by physical exam
- Must have a medical indication for treatment, as indicated by 1 of the following:
- Presence of constitutional symptoms that are attributed to lymphoma (e.g., B symptoms, including night sweats, fever, weight loss, fatigue, or pain)
- Lymphadenopathy that requires treatment based on presence of associated symptoms, potential threat to organ function (e.g., ureteric compromise from retroperitoneal disease), or degree of enlargement (i.e., > 5 cm)
- Impairment of normal organ function (e.g., impaired hematopoiesis due to marrow involvement by lymphoma or from splenomegaly and hypersplenism)
- Immune-related complications of lymphoma that require therapy
- Rate of disease progression for which observation is deemed inappropriate
- No history of any other lymphoproliferative disorder or evidence of transformation to an aggressive histology lymphoma
- No known CNS involvement by lymphoma
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Platelet count ≥ 75,000/mm^3*
- Absolute neutrophil count ≥ 1,000/mm^3*
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)
- Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French
- Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study
- No history of other malignancies, except for the following:
- Adequately treated nonmelanoma skin cancer
- Curatively treated in situ cancer of the cervix
- Ductal carcinoma in situ of the breast (as long as radiation limitation is not exceeded)
- Other solid tumors curatively treated with no evidence of disease for > 5 years
- No history of allergic reactions attributed to compounds containing boron or mannitol
- No history of an unusual or severe allergic reaction to rituximab or similar agent
- No pre-existing neuropathy ≥ grade 2
- No known HIV infection
- No other serious illness or medical condition that would preclude study participation, including any of the following:
- Active, uncontrolled bacterial, fungal, or viral infection
- Significant cardiac dysfunction
- Cardiovascular disease NOTE: *Exceptions will be allowed for values below these thresholds in patients with marrow involvement by lymphoma or lymphoma-related hypersplenism
PRIOR CONCURRENT THERAPY:
- No prior systemic therapy for lymphoma
- No prior bortezomib, cyclophosphamide, or vincristine
- At least 4 weeks since prior radiotherapy that involved ≤ 25% of functioning bone marrow and recovered
- Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy or if the irradiated field is not a significant marrow-bearing area
- At least 2 weeks since prior major surgery
- No other concurrent anticancer therapy, investigational agents, corticosteroids (except for physiologic replacement or antiemesis), cytotoxic chemotherapy, or immunotherapy
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Canada19 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Regional Cancer Program of the Hopital Regional
Greater Sudbury, Ontario, P3E 5J1
Hopital Charles LeMoyne
Greenfield Park, Quebec, J4V 2H1
QEII Health Sciences Center
Halifax, Nova Scotia, B3H 1V7
London Regional Cancer Program
London, Ontario, N6A 4L6
Credit Valley Hospital
Mississauga, Ontario, L5M 2N1
The Moncton Hospital
Moncton, New Brunswick, E1C 6Z8
CHUM - Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
McGill University - Dept. Oncology
Montreal, Quebec, H2W 1S6
CHA-Hopital Du St-Sacrement
Québec, Quebec, G1S 4L8
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, V3V 1Z2
Thunder Bay Regional Health Science Centre
Thunder Bay, Ontario, P7B 6V4
Odette Cancer Centre
Toronto, Ontario, M4N 3M5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Humber River Regional Hospital
Toronto, Ontario, M9N 1N8
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
BCCA - Vancouver Island Cancer Centre
Victoria, British Columbia, V8R 6V5
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
Official title: A Multi-Centre Phase II Trial Investigating the Efficacy and Tolerability of Bortezomib Added to Cyclophosphamide, Vincristine, Prednisone, and Rituximab (BCVP-R) for Patients With Advanced Stage Follicular Non-Hodgkin's Lymphoma Requiring Systemic First-Line Treatment
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with combination chemotherapy and rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with combination chemotherapy and rituximab works when given as first-line therapy in treating patients with stage III or stage IV follicular non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- Assess the efficacy of systemic first-line treatment comprising bortezomib, cyclophosphamide, vincristine, prednisone, and rituximab, in terms of complete response rate, in patients with stage III or IV follicular non-Hodgkin's lymphoma.
- Assess the incidence of severe neurotoxicity (defined as grade 3 or 4 neuropathy or neuropathic pain during the first 4 courses of treatment) in patients treated with this regimen.
Secondary
- Assess the overall response rate and response duration in patients treated with this regimen.
- Determine progression-free and overall survival of patients treated with this regimen.
- Evaluate the tolerability and characterize the toxicity profile of this regimen in these patients.
- Assess quality of life, with particular focus on neurotoxicity-related changes, of patients treated with this regimen.
OUTLINE: This is a multicenter, nonrandomized, open-label study.
Patient receive cyclophosphamide IV over 15-45 minutes, vincristine IV over 3-5 seconds and rituximab IV over 1½-6 hours on day 1, oral prednisone daily on days 1-5, and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, at the end of each course of treatment, and on day 42 at the post treatment visit.
After completion of study treatment, patients are followed at 3 and 6 weeks and then every 3-6 months thereafter.
PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
- Conditions
- Lymphoma
- Being tested
- rituximab, bortezomib, cyclophosphamide, prednisone, vincristine sulfate
- Keywords
- stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
375mg/m2 day 1
bortezomibDrug
1.3mg/m2 days 1 \& 8
cyclophosphamideDrug
750mg/m2 day 1
prednisoneDrug
40mg/m2 days 1-5
1.4mg/m2 day 1 (dose capped at 2mg)
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib + BCVP-R | Experimental | BCVP-R - q 21 days x 4 cycles Bortezomib: 1.3 mg/m2 Days 1 \& 8 Cyclophosphamide: 750 mg/m2 IV Day 1 Vincristine: 1.4 mg/m2 IV Day 1 (dose capped at 2 mg) Prednisone: 40 mg/m2 po Days 1-5 Rituximab: 375 mg/m2 IV Day 1 Receives: Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
Measured: 5 years
Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment
Measured: 5 years
Secondary outcomes (6)
Overall response rate
Measured: 5 years
Response duration in patients with observed responses
Measured: 5 years
Time to progression
Measured: 5 years
Overall survival
Measured: 5 years
Toxicity
Measured: 5 years
Quality of life
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2007 (estimated)
- Study start1 May 2007
- Primary completionApr 2011
- Study completion6 Jan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- NCIC Clinical Trials Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Laurie Sehn, Study chair, British Columbia Cancer AgencyMichael R. Crump, MD, FRCPC, Study chair, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428142
- Sponsor's protocol ID
- LY13
- Other IDs
- CAN-NCIC-LY13, CDR0000527275
- Status last verified
- Nov 2012
- First submitted
- 25 Jan 2007
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sehn LH, Macdonald DA, Rubin SH, et al.: Tolerability and efficacy of bortezomib added to CVP-R for previously untreated advanced stage follicular fymphoma: interim analysis of a phase II study by the NCIC Clinical Trials Group. [Abstract] Blood 112 (11): A-1576, 2008.
Sehn LH, MacDonald D, Rubin S, Cantin G, Rubinger M, Lemieux B, Basi S, Imrie K, Gascoyne RD, Sussman J, Chen BE, Djurfeldt M, Shepherd L, Couban S, Crump M. Bortezomib ADDED to R-CVP is safe and effective for previously untreated advanced-stage follicular lymphoma: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2011 Sep 1;29(25):3396-401. doi: 10.1200/JCO.2010.33.6594. Epub 2011 Aug 1.
PubMed 21810681
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Centre Phase II Trial Investigating the Efficacy and Tolerability of Bortezomib Added to Cyclophosphamide, Vincristine, Prednisone, and Rituximab (BCVP-R) for Patients With Advanced Stage Follicular Non-Hodgkin's Lymphoma Requiring Systemic First-Line Treatment
- ClinicalTrials.gov ID
- NCT00428142
- Acronym / sponsor ID
- LY13
- Conditions
- Lymphoma
- Keywords
- stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- NCIC Clinical Trials GroupResearch network
- Study start
- 1 May 2007 (actual)
- Primary completion
- Apr 2011 (actual)
- Study completion
- 6 Jan 2012 (actual)
- First posted
- 29 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with combination chemotherapy and rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with combination chemotherapy and rituximab works when given as first-line therapy in treating patients with stage III or stage IV follicular non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
Primary
- Assess the efficacy of systemic first-line treatment comprising bortezomib, cyclophosphamide, vincristine, prednisone, and rituximab, in terms of complete response rate, in patients with stage III or IV follicular non-Hodgkin's lymphoma.
- Assess the incidence of severe neurotoxicity (defined as grade 3 or 4 neuropathy or neuropathic pain during the first 4 courses of treatment) in patients treated with this regimen.
Secondary
- Assess the overall response rate and response duration in patients treated with this regimen.
- Determine progression-free and overall survival of patients treated with this regimen.
- Evaluate the tolerability and characterize the toxicity profile of this regimen in these patients.
- Assess quality of life, with particular focus on neurotoxicity-related changes, of patients treated with this regimen.
OUTLINE: This is a multicenter, nonrandomized, open-label study.
Patient receive cyclophosphamide IV over 15-45 minutes, vincristine IV over 3-5 seconds and rituximab IV over 1½-6 hours on day 1, oral prednisone daily on days 1-5, and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, at the end of each course of treatment, and on day 42 at the post treatment visit.
After completion of study treatment, patients are followed at 3 and 6 weeks and then every 3-6 months thereafter.
PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib + BCVP-R | Experimental | Biological: rituximab, Drug: bortezomib, Drug: cyclophosphamide, Drug: prednisone, Drug: vincristine sulfateBCVP-R - q 21 days x 4 cycles Bortezomib: 1.3 mg/m2 Days 1 \& 8 Cyclophosphamide: 750 mg/m2 IV Day 1 Vincristine: 1.4 mg/m2 IV Day 1 (dose capped at 2 mg) Prednisone: 40 mg/m2 po Days 1-5 Rituximab: 375 mg/m2 IV Day 1 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| rituximab375mg/m2 day 1 | Biological | Bortezomib + BCVP-R |
| bortezomib1.3mg/m2 days 1 \& 8 | Drug | Bortezomib + BCVP-R |
| cyclophosphamide750mg/m2 day 1 | Drug | Bortezomib + BCVP-R |
| prednisone40mg/m2 days 1-5 | Drug | Bortezomib + BCVP-R |
| vincristine sulfate1.4mg/m2 day 1 (dose capped at 2mg) | Drug | Bortezomib + BCVP-R |
Primary outcome
Complete response rate
Time frame: 5 years
Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment
Time frame: 5 years
6 secondary outcomes
Overall response rate
Time frame: 5 years
Response duration in patients with observed responses
Time frame: 5 years
Time to progression
Time frame: 5 years
Overall survival
Time frame: 5 years
Toxicity
Time frame: 5 years
Quality of life
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Results publicationSehn LH, Macdonald DA, Rubin SH, et al.: Tolerability and efficacy of bortezomib added to CVP-R for previously untreated advanced stage follicular fymphoma: interim analysis of a phase II study by the NCIC Clinical Trials Group. [Abstract] Blood 112 (11): A-1576, 2008.
- Results publication: PubMed 21810681Sehn LH, MacDonald D, Rubin S, Cantin G, Rubinger M, Lemieux B, Basi S, Imrie K, Gascoyne RD, Sussman J, Chen BE, Djurfeldt M, Shepherd L, Couban S, Crump M. Bortezomib ADDED to R-CVP is safe and effective for previously untreated advanced-stage follicular lymphoma: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2011 Sep 1;29(25):3396-401. doi: 10.1200/JCO.2010.33.6594. Epub 2011 Aug 1.
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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.
Laurie Sehn study chair
British Columbia Cancer Agency
Michael R. Crump, MD, FRCPC study chair
Princess Margaret Hospital, Canada
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab, bortezomib and cyclophosphamide in people with Lymphoma, run by NCIC Clinical Trials Group at 19 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 rate (time frame: 5 years). The study lists 2 primary outcomes in all. 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 NCT00428142, which also lists 2 linked publications.
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 27 Mar 2026.