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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00428142
Recruitment Status : Completed
First Posted : January 29, 2007
Last Update Posted : November 27, 2012
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: bortezomib Drug: cyclophosphamide Drug: prednisone Drug: vincristine sulfate Phase 2

Detailed Description:



  • 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.


  • 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  (Clinical Trial)
Actual Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : December 2006
Actual Primary Completion Date : April 2011
Actual Study Completion Date : January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma Steroids

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)

Primary Outcome Measures :
  1. Complete response rate [ Time Frame: 5 years ]
  2. Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 5 years ]
  2. Response duration in patients with observed responses [ Time Frame: 5 years ]
  3. Time to progression [ Time Frame: 5 years ]
  4. Overall survival [ Time Frame: 5 years ]
  5. Toxicity [ Time Frame: 5 years ]
  6. Quality of life [ Time Frame: 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00428142

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

Publications of Results:
Responsible Party: NCIC Clinical Trials Group Identifier: NCT00428142     History of Changes
Other Study ID Numbers: LY13
CDR0000527275 ( Other Identifier: PDQ )
First Posted: January 29, 2007    Key Record Dates
Last Update Posted: November 27, 2012
Last Verified: November 2012

Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):
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

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Tubulin Modulators