Clinical trial NCT00045695: Bortezomib in Treating Patients With Waldenstrom's Macroglobulinemia
Official title: A Phase II Study Of PS-341 (NSC 681239) In Patients With Untreated Or Relapsed Waldenstrom's Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: Waldenstrom macroglobulinemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response rate
timeFrame: 4 years
Secondary outcomes:
measure: Toxicity
timeFrame: 4 years
measure: Cytogenetics and genome profiling
timeFrame: 4 years
Other outcomes:
Locations:
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Christine I. Chen, MD
role: STUDY_CHAIR
References:
citation: 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 macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 Apr 20;25(12):1570-5. doi: 10.1200/JCO.2006.07.8659. Epub 2007 Mar 12.
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.