Bortezomib in Treating Patients With Waldenstrom's Macroglobulinemia

This study has been completed.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI) ( NCIC Clinical Trials Group )
ClinicalTrials.gov Identifier:
NCT00045695
First received: September 6, 2002
Last updated: May 16, 2013
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of PS-341 (NSC 681239) In Patients With Untreated Or Relapsed Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    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.

  • Cytogenetics and genome profiling [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To assess bone marrow and peripheral blood for cytogenetics and genome profiling by microarray in patients with Waldenstrom's macroglobulinemia.


Enrollment: 27
Study Start Date: August 2002
Study Completion Date: December 2009
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bortezomib
    PS-341 bolus intravenous injection twice weekly* for 2 out of every 3 weeks
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045695

Locations
United States, Illinois
Hinsdale Hematology Oncology Associates
Hinsdale, Illinois, United States, 60521
United States, Pennsylvania
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Cancer Care Ontario-London Regional Cancer Centre
London, Ontario, Canada, N6A 4L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Toronto Sunnybrook Regional Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Canada, Saskatchewan
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
NCIC Clinical Trials Group
Eastern Cooperative Oncology Group
Investigators
Study Chair: Christine I. Chen, MD Princess Margaret Hospital, Canada
  More Information

Additional Information:
Publications:
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.

Responsible Party: National Cancer Institute (NCI) ( NCIC Clinical Trials Group )
ClinicalTrials.gov Identifier: NCT00045695     History of Changes
Other Study ID Numbers: I152, CAN-NCIC-IND152, ECOG-JI152, NCI-NCIC-152, CDR0000257042
Study First Received: September 6, 2002
Last Updated: May 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
Waldenstrom macroglobulinemia

Additional relevant MeSH terms:
Lymphoma
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014