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

NCT ID: NCT00428142

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-01
• Study Completion Date: 2012-01-06

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

375mg/m2 day 1

bortezomib

Intervention Type: DRUG

1.3mg/m2 days 1 \& 8

cyclophosphamide

Intervention Type: DRUG

750mg/m2 day 1

prednisone

Intervention Type: DRUG

40mg/m2 days 1-5

vincristine sulfate

Intervention Type: DRUG

1.4mg/m2 day 1 (dose capped at 2mg)

Interventions

rituximab

375mg/m2 day 1

Intervention Type: BIOLOGICAL

bortezomib

1.3mg/m2 days 1 \& 8

Intervention Type: DRUG

cyclophosphamide

750mg/m2 day 1

Intervention Type: DRUG

prednisone

40mg/m2 days 1-5

Intervention Type: DRUG

vincristine sulfate

1.4mg/m2 day 1 (dose capped at 2mg)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurie Sehn

Role: STUDY_CHAIR

British Columbia Cancer Agency

Michael R. Crump, MD, FRCPC

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

Locations

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

QEII Health Sciences Center

Halifax, Nova Scotia, Canada

Regional Cancer Program of the Hopital Regional

Greater Sudbury, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Humber River Regional Hospital

Toronto, Ontario, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Countries

Canada

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 21810681 (View on PubMed)

Other Identifiers

CAN-NCIC-LY13

Identifier Type: -

Identifier Source: secondary_id

CDR0000527275

Identifier Type: OTHER

Identifier Source: secondary_id

LY13

Identifier Type: -

Identifier Source: org_study_id