A Phase II Study of Bortezomib and Gemcitabine in Patients With Relapsed Mantle Cell Lymphoma
A Phase II Study of Bortezomib and Gemcitabine in Patients With Relapsed Mantle Cell Lymphoma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may help gemcitabine work better by making cancer cells more sensitive to the drug.
PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with relapsed mantle cell lymphoma.
OBJECTIVES:
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
Not refractory to prior 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:
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:
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
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