Bortezomib, Combination Chemotherapy, and Rituximab as First-Line Therapy in Treating Patients With Stage III or Stage IV Follicular Non-Hodgkin's Lymphoma

March 23, 2026 updated by: NCIC Clinical Trials Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

95

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Surrey, British Columbia, Canada, V3V 1Z2
        • BCCA - Fraser Valley Cancer Centre
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BCCA - Vancouver Cancer Centre
      • Victoria, British Columbia, Canada, V8R 6V5
        • BCCA - Vancouver Island Cancer Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • The Moncton Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • QEII Health Sciences Center
    • Ontario
      • Greater Sudbury, Ontario, Canada, P3E 5J1
        • Regional Cancer Program of the Hopital Regional
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Mississauga, Ontario, Canada, L5M 2N1
        • Credit Valley Hospital
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Thunder Bay Regional Health Science Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Odette Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Univ. Health Network-Princess Margaret Hospital
      • Toronto, Ontario, Canada, M9N 1N8
        • Humber River Regional Hospital
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Hopital Charles LeMoyne
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM - Hopital Notre-Dame
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University - Dept. Oncology
      • Québec, Quebec, Canada, G1S 4L8
        • CHA-Hopital Du St-Sacrement
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bortezomib + BCVP-R
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
Biological: rituximab
375mg/m2 day 1
Drug: bortezomib
1.3mg/m2 days 1 & 8
Drug: cyclophosphamide
750mg/m2 day 1
Drug: prednisone
40mg/m2 days 1-5
Drug: vincristine sulfate
1.4mg/m2 day 1 (dose capped at 2mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete response rate
Time Frame: 5 years
5 years
Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 5 years
5 years
Time to progression
Time Frame: 5 years
5 years
Quality of life
Time Frame: 5 years
5 years
Overall response rate
Time Frame: 5 years
5 years
Toxicity
Time Frame: 5 years
5 years
Response duration in patients with observed responses
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Investigators

  • Study Chair: Michael R. Crump, MD, FRCPC, Princess Margaret Hospital, Canada
  • Study Chair: Laurie Sehn, British Columbia Cancer Agency

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2007

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

January 6, 2012

Study Registration Dates

First Submitted

January 25, 2007

First Submitted That Met QC Criteria

January 25, 2007

First Posted (Estimated)

January 29, 2007

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 23, 2026

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LY13
  • CAN-NCIC-LY13
  • CDR0000527275 (Other Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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