A Phase I Study Evaluating Combined Zevalin (Ibritumomab Tiuxetan) and Valcade (Bortezomib) in Relapsed/Refractory Low-Grade or Follicular B-Cell and Mantle Cell Lymphoma
A Phase I Study Evaluating Combined Zevalin (Ibritumomab Tiuxetan) and Valcade (Bortezomib) in Relapsed/Refractory Low-Grade or Follicular B-Cell and Mantle Cell Lymphoma
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, and radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving bortezomib together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with relapsed or refractory low-grade, follicular, or mantle cell non-Hodgkin's lymphoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of bortezomib.
Patients receive rituximab IV over 4 hours followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 to assess biodistribution. Patients without altered biodistribution receive rituximab IV over 4 hours followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients also receive bortezomib IV over 3-5 seconds on days 4, 8, 11, and 15.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients may be treated at the MTD.
After completion of study treatment, patients are followed every 3 months for 18 months and then every 6 months thereafter.
DISEASE CHARACTERISTICS:
Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma
Bone marrow biopsy required for pretreatment evaluation
Relapsed or refractory disease as defined by disease progression after initial complete response (CR) or failure to achieve CR
No bone marrow involvement ≥ 25% within the past 30 days
No pleural effusion or significant ascites
No active CNS involvement
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Life expectancy ≥ 3 months
Platelet count ≥ 100,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
AST ≤ 2.5 times upper limit of normal (ULN)
Total bilirubin ≤ 2.5 times ULN
Creatinine clearance ≥ 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Hepatitis B surface antigen negative
No current infection with hepatitis B virus
No HIV positivity
No neuropathy or neuropathic pain ≥ grade 2
No history of allergic reaction to boron or mannitol
No active serious infection or medical or psychiatric illness that would preclude study therapy
No other malignancy within the past 5 years except for the following:
No other condition, including any of the following:
PRIOR CONCURRENT THERAPY:
Recovered from all prior therapy
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgical resection of malignancy
More than 4 weeks since prior major surgery
More than 14 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
More than 14 days since prior and no other concurrent investigational agents
No prior radioimmunotherapy