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.

Eligibility 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