Bortezomib in Treating Patients With Mantle Cell Lymphoma

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 relapsed mantle cell lymphoma.

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.

• Belch A, Kouroukis C, Crump M, Sehn L, Gascoyne R, Klasa R, Powers J, Wright J, Eisenhauer E. A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150. Ann Oncol. 2007 Jan;18(1):116-21. Epub 2006 Sep 13.
• Belch A, Kouroukis CT, Crump M: Phase II trial of bortezomib in mantle cell lymphoma. [Abstract] Blood 104(11): A-608, 2004.
• Assouline S, Belch A, Sehn L, et al.: A phase II study of bortezomib in patients with mantle cell lymphoma. [Abstract] Blood 102 (11 Pt 1): A-3358, 2003.

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