Bortezomib in Treating Patients With Waldenstrom's Macroglobulinemia

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Bortezomib may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have untreated or relapsed Waldenstrom's macroglobulinemia.

Detailed Description
-----------------
OBJECTIVES: Determine the efficacy of bortezomib, in terms of response rate, in patients with previously untreated or relapsed Waldenstrom's macroglobulinemia. Determine the toxicity of this drug in these patients. Determine the time to progression, stable disease duration, and response duration in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks. Patients with complete or partial response or stable disease are followed every 3 months thereafter. PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 1.5-2 years.

Official Title
-----------------
A Phase II Study Of PS-341 (NSC 681239) In Patients With Untreated Or Relapsed Waldenstrom's Macroglobulinemia

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Drug: bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Diagnosis of Waldenstrom's macroglobulinemia confirmed by immunofixation or immunoelectrophoresis Newly diagnosed or untreated with IgM ≥ 20 g/L OR Previously treated with IgM ≥ 5 g/L Non-refractory, defined as no disease progression during prior therapy or within 4 weeks of the last dose of most recent prior therapy (12 weeks for rituximab) Must have 1 or more of the following: Symptomatic lymphadenopathy Hepatomegaly and/or splenomegaly Anemia (i.e., hemoglobin < 11.0 g/dL) Hyperviscosity syndrome No other lymphoproliferative disease including transformed aggressive lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic See Disease Characteristics Absolute granulocyte count ≥ 1,000/mm^3 Platelet count ≥ 50,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Other No uncontrolled bacterial, fungal, or viral infection No pre-existing sensory or motor neurotoxicity grade 2 or greater No other prior malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor for which patient has been disease free for at least 5 years No other serious illness or medical condition that would preclude study participation No unreasonable geographical limitations Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy See Chemotherapy See Disease Characteristics At least 12 weeks since prior rituximab (for patients who have progressed) At least 24 weeks since prior rituximab (for patients who have not progressed) No prior high-dose chemotherapy and stem cell transplantation No prior radioactive monoclonal antibodies Chemotherapy See Disease Characteristics See Biologic therapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) No more than 2 prior chemotherapy regimens The same chemotherapy combination given for first-line and second-line therapy is considered 2 regimens Single-agent rituximab not considered 1 prior regimen No concurrent cytotoxic chemotherapy Endocrine therapy No concurrent corticosteroids Radiotherapy At least 4 weeks since prior radiotherapy (except for low-dose, non- myelosuppressive radiotherapy) and recovered No prior radiotherapy to more than 25% of bone marrow Surgery At least 4 weeks since prior major surgery Other At least 4 weeks since prior plasmapheresis At least 4 weeks since prior investigational anticancer therapy No other concurrent investigational anticancer agents or therapies

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|PS-341 bolus intravenous injection twice weekly* for 2 out of every 3 weeks|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | To assess the efficacy (response rate) of PS-341 given as a bolus intravenous injection twice weekly for two out of every 3 weeks in the treatment of a population of patients with previously untreated or relapsed Waldenström's Macroglobulinemia | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | To assess the toxicity of PS-341 in patients with Waldenström's Macroglobulinemia as well as time to progression, stable disease duration and, if responses are observed, response duration. | 4 years | 
| Cytogenetics and genome profiling | To assess bone marrow and peripheral blood for cytogenetics and genome profiling by microarray in patients with Waldenstrom's macroglobulinemia. | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Waldenstrom macroglobulinemia