Bortezomib in Treating Patients With Waldenstrom's Macroglobulinemia

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045695
• Other study ID #: I152
• Secondary ID: CAN-NCIC-IND152E
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2002
• Last updated: May 16, 2013
• Start date: August 2002
• Est. completion date: December 2009

Study information

• Verified date: September 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 2009
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• bortezomib
PS-341 bolus intravenous injection twice weekly* for 2 out of every 3 weeks

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Abramson Cancer Center at the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Chen CI, Kouroukis CT, White D, Voralia M, Stadtmauer E, Stewart AK, Wright JJ, Powers J, Walsh W, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglob — View Citation

Chen CI, White Darrell, Kouroukis TC, et al.: Antitumor activity of bortezomib (PS-341; Velcade) in a phase II study of patients with previously untreated or treated Waldenstrom's macroglobulinemia (WM). [Abstract] Blood 104 (11): A-3278, 2004.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No