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 low-grade lymphoproliferative disorders.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma Chronic Lymphocytic Leukemia indolent or aggressive adult non-Hodgkin's lymphoma	Drug: bortezomib  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the frequency and duration of complete and partial response rates in patients with low-grade lymphoproliferative disorders treated with bortezomib.
• Determine the pharmacodynamics of this regimen in these patients.
• Determine the response of minimal residual disease by polymerase chain reaction (PCR) detectable or clonotypic PCR minimal residual disease in bone marrow of patients treated with this regimen.
• Determine the time to progression and overall survival of patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to disease type (follicular lymphoma vs mantle cell lymphoma vs marginal zone and small lymphocytic lymphomas and chronic lymphocytic leukemia).

Patients receive bortezomib IV twice weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.

Patients are followed every 3 months for 1 year and then every 4 months for 2 years.

PROJECTED ACCRUAL: Approximately 18-70 patients (6-23 per stratum) will be accrued for this study within 9-18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed low-grade lymphoproliferative disorder
• Relapsed or refractory chronic lymphocytic leukemia (CLL)
• Relapsed or refractory B-cell small lymphocytic lymphoma
• Relapsed or refractory marginal zone lymphoma
• Relapsed or refractory grade I, II, or III follicular center cell lymphoma
• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory Waldenstrom's macroglobulinemia
• Measurable disease for non-Hodgkin's lymphoma (NHL) only
• At least 1 unidimensionally measurable lesion
• At least 2 cm by conventional techniques OR at least 1 cm by spiral CT scan
• Lymph nodes no greater than 1 cm in short axis considered normal
• Absolute lymphocytosis greater than 5,000/mm^3 with B-cell phenotype (CD19, 20, or 23 positive) with more than 30% bone marrow lymphocytes for CLL or other leukemic forms of NHL
• No known brain metastases NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count greater than 1,500/mm^3 (500/mm^3 if lymphomatous involvement of bone marrow)
• Platelet count greater than 50,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN (4 times ULN in case of liver metastases)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No symptomatic congestive heart failure
• No New York Heart Association class III or IV heart disease
• No unstable angina pectoris
• No cardiac arrhythmia
• No myocardial infarction within the past 6 months
• No cerebrovascular accident or transient ischemic attack within the past 6 months
• No history of orthostatic hypotension
• No evidence of acute ischemia or significant conduction abnormality (left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular blocks) on electrocardiogram
• No uncontrolled hypertension requiring antihypertensive medication

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Febrile episodes up to 38.5°C allowed if no evidence of active infection
• No other uncontrolled concurrent illness
• No known or active HIV infection
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study entry

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)

Chemotherapy:

• No more than 3 prior regimens of conventional cytotoxic chemotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

• At least 1 week since prior steroid therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No other concurrent investigational agents

Illinois
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611-3013,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-7284,  United States; Recruiting

Study chairs or principal investigators

Owen A. O'Connor, MD, PhD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000068860; MSKCC-01049; NCI-2795; CWRU-MSKCC-1Y02; UNMC-03903; NCT00023764
Record last reviewed:  July 2003
Last Updated:  December 6, 2004
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00023764
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08