Bortezomib and Gemcitabine in Treating Patients With Relapsed Mantle Cell Lymphoma

OBJECTIVES:

• Determine the efficacy (response rate) of bortezomib and gemcitabine hydrochloride in patients with relapsed mantle cell lymphoma.
• Determine the toxicity of this regimen in these patients.
• Determine the time to progression and duration of response in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until relapse/progression.

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma

• Relapsed disease
• Not refractory to prior therapy

• Must have received 1-3 prior systemic chemotherapy regimens AND has had no disease progression while receiving chemotherapy or within 1 month of last dose of most recent therapy
• Clinically and/or radiologically documented disease

• At least 1 site of disease must be bidimensionally measurable by CT scan or MRI with ≥ 1 lesion meeting 1 of the following criteria:

• Lymph nodes ≥ 1.5 cm x 1.5 cm by spiral CT scan
• Non-nodal lesion ≥ 1 cm x 1 cm by MRI, CT scan, or physical exam
• No nonmeasurable disease only
• No preexisting ascites or pleural effusion ≥ grade 2
• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST or ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• LVEF ≥ 45% by echocardiogram or MUGA
• No history of allergic reactions attributed to compounds containing boron or mannitol
• No preexisting edema ≥ grade 2
• No preexisting neuropathy (sensory and/or pain) ≥ grade 2
• No preexisting shortness of breath ≥ grade 2
• No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• No other serious illness or medical condition that would preclude compliance with study requirements, including any of the following:

• Serious uncontrolled infection
• Uncontrolled or severe cardiovascular disease, including any of the following:

• Myocardial infarction within the past 6 months
• New York Heart Association class III-IV heart failure
• Uncontrolled angina
• Clinically significant pericardial disease
• Cardiac amyloidosis
• Significant neurological disorder

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 weeks since prior chemotherapy
• No prior radioactive monoclonal antibody therapy
• No prior bortezomib
• No prior investigational therapy (except for flavopiridol)
• No prior radiotherapy to > 25% of functioning bone marrow
• At least 4 weeks since prior radiotherapy and recovered

• Low-dose, nonmyelosuppressive radiotherapy may be allowed
• At least 2 weeks since prior major surgery
• No other concurrent anticancer therapy
• No concurrent corticosteroids
• No other concurrent cytotoxic chemotherapy
• No other concurrent investigational agents