Bortezomib in Treating Patients With Newly Diagnosed High-Risk Stage III Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00075881
First received: January 9, 2004
Last updated: November 27, 2012
Last verified: October 2012
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well bortezomib works in treating patients with newly diagnosed high-risk stage III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Plasma Cell Neoplasm
Drug: PS-341
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study Of PS-341 For Patients With High-Risk, Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response Rate on Induction [ Time Frame: participants were evaluated prior to each cycle, up to 8 cycles with a median number of 6 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    Eastern Cooperative Oncology Group (ECOG) Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 42 eligible and treated patients were included in the analysis.


Secondary Outcome Measures:
  • Response Rate on Maintenance [ Time Frame: participants were evaluated prior to each cycle, up to 45 cycles with a median number of 9 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    ECOG Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 15 eligible and treated patients were included in the analysis.

  • Response Rate on Reinduction [ Time Frame: participants were evaluated prior to each cycle, up to 23 cycles with a median number of 3 cycles. 1 cycle=21 days ] [ Designated as safety issue: No ]
    ECOG Myeloma Response Criteria that follows the standard European Group for Blood and Bone Marrow Transplant criteria was used to evaluate patient response and progression. Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have complete response. 7 eligible and treated patients were included in the analysis.

  • 1-year Progression Free Survival Probability [ Time Frame: Every 3 months if patient is <2 years from study entry, every 6 months if patient is 2-6 years from study entry, no specific requirment if patient is more than 6 years from study entry ] [ Designated as safety issue: No ]
    Progression-free survival is defined as time from randomization to disease progression or death from any cause, whichever occurred first. Disease progression is defined using the ECOG Myeloma Response Criteria. Kaplan-Meier method is used to estimate the 1-year progression-free survival probability. 42 eligible and treated patients were included in the analysis.


Enrollment: 44
Study Start Date: January 2004
Study Completion Date: May 2011
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PS-341

Induction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose. Repeat cycles every 3 weeks for a total of 8 cycles.

Maintenance treatment: PS-341 1.3 mg/m2 IV push days 1 and 15

Reinduction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose.

Drug: PS-341

Induction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose. Repeat cycles every 3 weeks for a total of 8 cycles.

Maintenance treatment: PS-341 1.3 mg/m2 IV push days 1 and 15

Reinduction treatment: PS-341 1.3 mg/m2 IV push days 1, 4, 8, and 11. As per the PS-341 package insert, there should be at least 72 hours between each PS-341 dose.

Other Names:
  • Bortezomib
  • Velcade
  • MLN-341
  • LDP-341

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with newly diagnosed high-risk stage III multiple myeloma treated with bortezomib induction therapy.

Secondary

  • Determine the progression-free survival of patients treated with this drug.
  • Determine the response rate and duration of second response in patients who relapse or progress while on maintenance therapy and subsequently receive reinduction therapy with this drug.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression must complete at least 2 courses of induction therapy. Patients who achieve complete remission receive 2 additional courses, but no more than 8 courses total, and then proceed to maintenance therapy.
  • Maintenance therapy: Patients receive bortezomib IV over 3-5 seconds on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may return to induction therapy (reinduction therapy).
  • Reinduction therapy: Patients receive bortezomib as in induction therapy. Courses repeat every 3 weeks until second disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years from study entry.

ACTUAL ACCRUAL: A total of 44 patients were accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Diagnosis of multiple myeloma meeting the following criteria:

    • Symptomatic disease diagnosed within the past 30 days
    • Measurable or evaluable disease meeting at least 1 of the following criteria:

      • Serum monoclonal protein ≥ 1 g/dL (measurable disease)
      • Monoclonal light chain in urine protein electrophoresis ≥ 200 mg/24-hour urine collection (measurable disease)
      • Bone marrow plasmacytosis ≥ 30% (evaluable disease)
  • High-risk disease, defined by ≥ 1 of the following criteria:

    • Beta 2-microglobulin ≥ 5.5 μg/mL
    • Plasma cell labeling index ≥ 1%
    • Deletion of chromosome 13 by cytogenetic analysis
  • Age>=18
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (ECOG performance status of 3 allowed if secondary to acute bone event [i.e., fracture])
  • Adequate hematopoietic,hepatic, renal, cardiovascular function:

    • Platelet count ≥ 20,000/mm^3 (transfusion allowed)
    • Hemoglobin ≥ 7.0 g/dL (transfusion allowed)
    • Absolute neutrophil count ≥ 500/mm^3 (without growth factor support)
    • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 times ULN
    • Alkaline phosphatase ≤ 2.5 times ULN
    • Creatinine clearance ≥ 20 mL/min
  • Fertile patients must use effective contraception
  • Concurrent corticosteroids allowed for treatment of chronic disorders other than multiple myeloma (e.g., rheumatoid arthritis or adrenal insufficiency)
  • Prior or concurrent bisphosphonates allowed
  • Concurrent localized radiotherapy allowed upon approval by study chair

Exclusion criteria:

  • Pregnant or nursing
  • Positive pregnancy test
  • Myocardial infarction within the past 6 months
  • New York Heart Association class III or IV heart failure
  • Uncontrolled angina
  • Acute ischemia by electrocardiography (EKG)
  • Severe uncontrolled ventricular arrhythmias
  • Active conduction system abnormalities by EKG
  • Cardiac amyloidosis
  • Poorly controlled hypertension
  • History of allergic reaction attributable to compounds containing boron or mannitol
  • Greater than grade 1 peripheral neuropathy
  • Other serious medical or psychiatric illness that would preclude study completion
  • Prior biologic therapy for multiple myeloma
  • Concurrent biologic therapy
  • Concurrent pegfilgrastim
  • Prior chemotherapy for multiple myeloma
  • Concurrent chemotherapy
  • Prior radiotherapy for multiple myeloma
  • Less than 4 weeks since prior radiotherapy for plasmacytoma (e.g., solitary plasmacytoma)
  • Other concurrent antineoplastic therapy for multiple myeloma
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00075881

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
United States, Arizona
CCOP - Mayo Clinic Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Veterans Affairs Medical Center - Palo Alto
Palo Alto, California, United States, 94304-1290
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305-5216
United States, Colorado
CCOP - Colorado Cancer Research Program, Incorporated
Denver, Colorado, United States, 80224
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
MBCCOP - Howard University Cancer Center
Washington, District of Columbia, United States, 20060
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0277
Veterans Affairs Medical Center - Gainesville
Gainesville, Florida, United States, 32608-1197
Veterans Affairs Medical Center - Miami
Miami, Florida, United States, 33125
Martin Memorial Cancer Center
Stuart, Florida, United States, 34994
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
Veterans Affairs Medical Center - Tampa (Haley)
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
Veterans Affairs Medical Center - Lakeside Chicago
Chicago, Illinois, United States, 60611-4494
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
CCOP - Evanston
Evanston, Illinois, United States, 60201
Hinsdale Hematology Oncology Associates
Hinsdale, Illinois, United States, 60521
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615-7828
Swedish-American Regional Cancer Center
Rockford, Illinois, United States, 61104-2315
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
Veterans Affairs Medical Center - Indianapolis (Roudebush)
Indianapolis, Indiana, United States, 46202
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316-2301
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Burgess Health Center
Onawa, Iowa, United States, 51040
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
United States, Louisiana
CCOP - Ochsner
New Orleans, Louisiana, United States, 70121
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Cancer Center at Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417-2399
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, Nebraska
Veterans Affairs Medical Center - Omaha
Omaha, Nebraska, United States, 68105
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Midlands Cancer Center at Midlands Community Hospital
Papillion, Nebraska, United States, 68128-4157
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Veterans Affairs Medical Center - East Orange
East Orange, New Jersey, United States, 07018
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
MBCCOP-Our Lady of Mercy Cancer Center
Bronx, New York, United States, 10466
Veterans Affairs Medical Center - Brooklyn
Brooklyn, New York, United States, 11209
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
Veterans Affairs Medical Center - New York
New York, New York, United States, 10010
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
MetroHealth's Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
CCOP - Columbus
Columbus, Ohio, United States, 43206
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
United States, Oklahoma
CCOP - Oklahoma
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Hahnemann University Hospital
Philadelphia, Pennsylvania, United States, 19102-1192
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15236
Veterans Affairs Medical Center - Pittsburgh
Pittsburgh, Pennsylvania, United States, 15240
CCOP - MainLine Health
Wynnewood, Pennsylvania, United States, 19096
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Tennessee
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232-6307
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
Nashville, Tennessee, United States, 37212-2637
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Veterans Affairs Medical Center - Madison
Madison, Wisconsin, United States, 53705
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-0001
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226-3596
Veterans Affairs Medical Center - Milwaukee (Zablocki)
Milwaukee, Wisconsin, United States, 53295
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Peru
Instituto de Enfermedades Neoplasicas
Lima, Peru, 34
Puerto Rico
MBCCOP - San Juan
San Juan, Puerto Rico, 00921-3201
San Juan City Hospital
San Juan, Puerto Rico, 00936-7344
Veterans Affairs Medical Center - San Juan
San Juan, Puerto Rico, 00927-5800
South Africa
Pretoria Academic Hospital
Pretoria, South Africa, 0001
Sponsors and Collaborators
Investigators
Study Chair: Angela Dispenzieri, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Dispenzieri A, Zhang L, Fonseca R, et al.: Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02). [Abstract] Blood 108 (11): A-3527, 2006.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075881     History of Changes
Other Study ID Numbers: CDR0000349450, U10CA021115, E2A02
Study First Received: January 9, 2004
Results First Received: March 8, 2012
Last Updated: November 27, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage III multiple myeloma
high risk, newly diagnosed multiple myeloma

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

ClinicalTrials.gov processed this record on April 23, 2014