Phase II Study of PS-341 in Low Grade Lymphoproliferative Disorders
Phase II Study of PS-341 in Low Grade Lymphoproliferative Disorders
Phase II trial to study the effectiveness of bortezomib in treating patients who have low-grade lymphoproliferative disorders. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.
PRIMARY OBJECTIVES:
I. Determine the frequency and duration of complete and partial response rates in patients with grade I, II, or III follicular lymphoma or mantle cell lymphoma treated with bortezomib.
SECONDARY OBJECTIVES:
I. 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.
II. Determine the time to progression and overall survival of patients treated with this regimen.
III. Determine the toxic effects of this regimen in these patients.
OUTLINE: Patients are stratified according to disease type (follicular lymphoma vs mantle cell lymphoma).
Patients receive an infusion of bortezomib over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 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.
Inclusion Criteria:
Histologically or cytologically confirmed lymphoproliferative disorder of 1 of the following subtypes:
* Relapsed or refractory grade I, II, or III follicular center cell lymphoma
Measurable disease for non-Hodgkin's lymphoma (NHL) only
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
Performance status - Karnofsky 70-100%
At least 3 months
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
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)
Creatinine less than 1.5 times ULN
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
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
At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)
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
At least 1 week since prior steroid therapy
At least 4 weeks since prior radiotherapy and recovered
At least 4 weeks since prior major surgery
No other concurrent investigational agents