Bortezomib and Rituximab in Treating Patients With Non-Hodgkin's Lymphoma

NCT00093769 | Completed Phase 2

• 3 other identifiers: CDR0000390235UCLA-0401054-01MILLENNIUM-M34103-061
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving bortezomib together with rituximab may kill more cancer cells. PURPOSE: This randomized phase II trial is studying how well giving bortezomib together with rituximab works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent marginal zone lymphoma; splenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Response rate (complete response [CR], CR-unconfirmed [CRu], and partial response [PR])

  12 weeks

Secondary Outcomes (3)

• Response rate (CR, CRu, and PR) at the first disease response evaluation

  12 weeks

• Overall CR rate (CR and CRu)

  12 weeks

• Safety and tolerability

  12 weeks

Study Arms (1)

bortezomib + rituximab

EXPERIMENTAL

Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 only and on day 1 of course 2 only. Treatment with repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15 and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 only. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients in either arm may crossover to the other arm if treatment is found to be ineffective.

Drug: bortezomib + rituximab

Interventions

bortezomib + rituximab DRUG

Arm I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 only and on day 1 of course 2 only. Treatment with repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15 and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 only. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients in either arm may crossover to the other arm if treatment is found to be ineffective.

bortezomib + rituximab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of indolent B-cell non-Hodgkin's lymphoma of 1 of the following subtypes: * Follicular (grade 1, 2, or 3) * Marginal zone (extranodal, nodal, or splenic) * CD20-positive disease * Relapsed or progressive disease after prior anti-neoplastic therapy, as indicated by 1 of the following: * New lesions * Objective evidence of progression of existing lesions * Complete response ≥ 6 months in duration after prior rituximab therapy\* NOTE: \*For patients who were previously treated with a regimen that included rituximab * At least 1 measurable lymph node mass \> 1.5 cm in 2 perpendicular dimensions that has not been irradiated OR that has progressed since prior radiotherapy * No active CNS lymphoma PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 50-100% OR * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 50,000/mm\^3 Hepatic * AST and ALT ≤ 3 times upper limit of normal (ULN) * Bilirubin ≤ 2 times ULN Renal * Creatinine ≤ 2 mg/dL OR * Creatinine clearance ≥ 30 mL/min Immunologic * No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or to any component of rituximab, including polysorbate 80 and sodium citrate dihydrate * No active systemic infection requiring treatment * No history of allergic reaction attributable to compounds containing boron or mannitol Other * No peripheral neuropathy or neuropathic pain ≥ grade 2 * No other malignancy within the past 5 years except completely resected basal cell or squamous cell skin cancer or an in situ malignancy * Previously diagnosed prostate cancer allowed provided the following criteria are met: * T1-2a, N0, M0 disease AND Gleason score ≤ 7 AND prostate specific antigen (PSA) ≤ 10 ng/mL before initial therapy * Treated with definitive curative therapy (i.e., prostatectomy or radiotherapy) within the past 2 years * No clinical evidence of prostate cancer AND undetectable PSA (for prostatectomy patients) or PSA \< 1 ng/mL (for patients who did not undergo prostatectomy) * No serious medical or psychiatric illness that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * More than 10 weeks since prior radioimmunoconjugates or toxin immunoconjugates (e.g., ibritumomab tiuxetan or iodine I 131 tositumomab) * More than 4 weeks since prior rituximab, alemtuzumab, or other unconjugated therapeutic antibody * No concurrent prophylactic bone marrow growth factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or epoetin alfa) during course 1 of study therapy Chemotherapy * More than 6 weeks since prior nitrosoureas * No concurrent cisplatin Endocrine therapy * No concurrent corticosteroids (e.g., dexamethasone) except prednisone ≤ 15 mg/day or equivalent for adrenal insufficiency Radiotherapy * See Disease Characteristics * See Biologic therapy * More than 3 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * More than 2 weeks since prior major surgery Other * Recovered from all prior therapy * No prior bortezomib * More than 3 weeks since prior antineoplastic therapy * More than 3 weeks since prior experimental therapy * No other concurrent antineoplastic therapy * No other concurrent investigational agents * Concurrent participation in a non-treatment study allowed provided it does not interfere with participation in this study

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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. doi: 10.1200/JCO.2008.17.7980. Epub 2009 Sep 21.

  PMID: 19770386 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

Bortezomib; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sven De Vos, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 6, 2004
• First Posted: October 8, 2004
• Study Start: August 1, 2004
• Primary Completion: August 1, 2005
• Last Updated: October 4, 2012

Record last verified: 2012-10

Locations

US (1)