RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have previously untreated or relapsedmantle cell lymphoma.

Condition	Treatment or Intervention	Phase
stage I mantle cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma recurrent mantle cell lymphoma	Drug: bortezomib  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of bortezomib, in terms of response rate, in patients with previously untreated or relapsed mantle cell lymphoma.
• Determine the toxicity of this drug in these patients.
• Correlate suppression of 20S proteasome levels with toxicity of and response to this drug in these patients.
• Determine the time to progression and response duration in patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response (CR) receive 2 courses beyond documentation of CR. Patients with stable disease receive a maximum of 4 courses. Patients with partial response (PR) continue therapy until disease progression or for 2 courses beyond documentation of stable PR.

Patients are followed at 4 weeks and then every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 18-24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed relapsed or untreated mantle cell lymphoma
• No refractory disease defined as progression while on chemotherapy or within 1 month after completion of chemotherapy
• At least 1 bidimensionally measurable disease site*
• Lymph nodes at least 1.5 cm by 1.5 cm by spiral CT scan OR
• Non-nodal lesions (e.g., skin lesion or nodules) at least 1 cm by 1 cm by MRI, CT scan, or physical exam NOTE: *Bone lesions are not considered bidimensionally measurable disease
• No pre-existing ascites or pleural effusion
• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• LVEF at least 45% by echocardiogram or MUGA

Pulmonary

• No pre-existing shortness of breath greater than grade 1

Other:

• No uncontrolled bacterial, fungal, or viral infections
• No pre-existing edema greater than grade 1
• No pre-existing neuropathy greater than grade 1
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other serious illness or medical condition that would preclude study compliance
• No geographical conditions that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Chemotherapy
• Prior rituximab allowed
• No prior radioactive monoclonal antibody therapy

Chemotherapy:

• See Disease Characteristics
• No prior high-dose chemotherapy with stem cell transplantation
• No more than 2 prior systemic chemotherapy regimens
• Same chemotherapy combination given for first-line and second-line therapy is considered 2 regimens
• No prior flavopiridol
• At least 6 weeks since prior chemotherapy
• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No prior radiotherapy to 25% or more of functioning bone marrow
• At least 4 weeks since prior radiotherapy (except low-dose nonmyelosuppressive radiotherapy) and recovered
• No concurrent radiotherapy to the sole site of measurable disease

Surgery:

• At least 2 weeks since prior major surgery

Other:

• No prior investigational therapy
• No other concurrent anticancer therapy
• No other concurrent investigational anticancer therapy

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency, Vancouver,  British Columbia,  V5Z 4E6,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

Andrew R. Belch, MD,  Study Chair,  Cross Cancer Institute   

Study ID Numbers:  CDR0000069207; CAN-NCIC-IND150
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030875
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08