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

NCT00428142 | Completed Phase 2 DMC

• 3 other identifiers: LY13CAN-NCIC-LY13CDR0000527275
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 19

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.

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

Outcome Measures

Primary Outcomes (2)

• Complete response rate

  5 years

• Incidence of severe grade 3 or 4 neurotoxicity or neuropathic pain during the first 4 courses of treatment

  5 years

Secondary Outcomes (6)

• Overall response rate

  5 years

• Response duration in patients with observed responses

  5 years

• Time to progression

  5 years

• Overall survival

  5 years

• Toxicity

  5 years

Study Arms (1)

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

Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate

Interventions

bortezomib DRUG

1.3mg/m2 days 1 \& 8

Bortezomib + BCVP-R

cyclophosphamide DRUG

750mg/m2 day 1

Bortezomib + BCVP-R

prednisone DRUG

40mg/m2 days 1-5

Bortezomib + BCVP-R

vincristine sulfate DRUG

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

Bortezomib + BCVP-R

rituximab BIOLOGICAL

375mg/m2 day 1

Bortezomib + BCVP-R

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (19)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Regional Cancer Program of the Hopital Regional

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Humber River Regional Hospital

Toronto, Ontario, M9N 1N8, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Related Publications (2)

• 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.

  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.

  PMID: 21810681 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular

Interventions

Rituximab; Bortezomib; Cyclophosphamide; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Laurie Sehn

  British Columbia Cancer Agency

  STUDY CHAIR

• Michael R. Crump, MD, FRCPC

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2007
• First Posted: January 29, 2007
• Study Start: May 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: January 6, 2012
• Last Updated: March 27, 2026

Record last verified: 2012-11

Locations

CA (19)