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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00428142
First received: January 25, 2007
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
Drug: bortezomib
Drug: cyclophosphamide
Drug: prednisone
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Response duration in patients with observed responses [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 95
Study Start Date: December 2006
Study Completion Date: January 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00428142

Locations
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
Humber River Regional Hospital
Toronto, Ontario, Canada, M9N 1N8
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
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
Investigators
Study Chair: Laurie Sehn British Columbia Cancer Agency
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Additional Information:
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.

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00428142     History of Changes
Other Study ID Numbers: LY13, CAN-NCIC-LY13, CDR0000527275
Study First Received: January 25, 2007
Last Updated: November 26, 2012
Health Authority: Canada: Health Canada

Keywords provided by 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
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Cyclophosphamide
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 20, 2014