Bortezomib, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory Low-Grade, Follicular, or Mantle Cell Non-Hodgkin's Lymphoma

UNC Lineberger Comprehensive Cancer Center

Status and phase

Completed

Phase 1

Conditions

Lymphoma

Treatments

Biological: rituximab

Drug: bortezomib

Radiation: Indium 111 ibritumomab tiuxetan

Radiation: yttrium Y 90 ibritumomab tiuxetan

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00334438

CDR0000550130 (Other Identifier)

LCCC 0525

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose (MTD) of bortezomib in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma.
Determine the dose-limiting toxicity of this regimen in these patients.

Secondary

Determine the response rate in patients treated with this regimen.

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.

Enrollment

12 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed low-grade, follicular B-cell, or mantle cell non-Hodgkin's lymphoma
- Bone marrow biopsy required for pretreatment evaluation
  - Unilateral bone marrow biopsy allowed
  - Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
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:
- Basal cell or squamous cell carcinoma of the skin that has been completely resected
- In situ malignancy that has been completely resected
- T1-T2a, N0, M0 prostate cancer treated with a prostatectomy or radiotherapy within the past 2 years with an undetectable PSA level
No other condition, including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class III-IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Electrocardiographic evidence of acute ischemia or active conduction system abnormalities

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
- No limitations on the number of prior therapies
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
- Concurrent participation in a nontreatment study allowed
No prior radioimmunotherapy