PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

An International, Multi-Center, Randomized, Open-Label Study of PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00048230
• Other study ID #: M34101-039
• Status: Completed
• Phase: Phase 3
• First received: October 28, 2002
• Last updated: January 12, 2012
• Start date: June 2002
• Est. completion date: December 2004

Study information

• Verified date: January 2012
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will compare the efficacy of PS-341 versus high dose dexamethasone.

Other known NCT identifiers

• NCT00052260

Recruitment information / eligibility

• Status: Completed
• Enrollment: 620
• Est. completion date: December 2004
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria

• Patient is of a legally consenting age, as defined by local regulations.

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

• Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

• Male patient agrees to use an acceptable method for contraception for the duration of the study.

• Patient was previously diagnosed with multiple myeloma based on standard criteria and currently requires second-, third-, or fourth-line therapy because of PD, defined as a 25% increase in M-protein, development of new or worsening of existing lytic bone lesions or soft tissue plasmacytomas, or hypercalcemia (serum calcium >11.5 mg/dL), or relapse from CR.

• Patient has measurable disease, defined as follows:

• For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value (generally, but not exclusively, greater than 1 g/dL of IgG M-Protein and greater than 0.5g/dL IgA) and, where applicable, urine light-chain excretion of =200 mg/24 hours.

• For oligo- or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan). In patients with oligosecretory multiple myeloma, the serum and/or urine M-protein measurements are very low and difficult to follow for response assessments. Therefore, other disease sites (bone marrow; extramedullary mass) must be assessed and followed. In patients with non-secretory multiple myeloma, there is no M-protein in serum or urine by immunofixation.

• Patient has a Karnofsky performance status =60%.

• Patient has a life-expectancy >3 months.

• Patient has the following laboratory values at and within 14 days before Baseline (Day 1 of Cycle 1, before study drug administration):

• Platelet count =50 x 10E+9/L without transfusion support within 7 days before the laboratory test.

• Hemoglobin =7.5 g/dL, without transfusion support within 7 days before the laboratory test.

• Absolute neutrophil count (ANC) =0.75 x 10E+9/L without the use of colony stimulating factors.

• Corrected serum calcium <14 mg/dL (3.5 mmol/L).

• Aspartate transaminase (AST): =2.5 x the upper limit of normal (ULN).

• Alanine transaminase (ALT): =2.5 x the ULN.

• Total bilirubin: =1.5 x the ULN.

• Calculated or measured creatinine clearance: =20 mL/minute.

Exclusion Criteria

• Patient previously received treatment with VELCADE.

• Patient previously was refractory to treatment with high-dose dexamethasone, as experiencing less than a partial response to or PD within 6 months after discontinuing dexamethasone, or discontinued dexamethasone because of =Grade 3 dexamethasone-related toxicity.

• Previous high-dose dexamethasone therapy is defined as >500 mg dexamethasone or equivalent over a 10-week period, whether administered alone or as part of the VAD regimen.

• Patient received nitrosoureas within 6 weeks or any other chemotherapy, including thalidomide or clarithromycin, or radiation therapy within 3 weeks before enrollment.

• Patient received corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks before enrollment.

• Patient received immunotherapy or antibody therapy within 8 weeks before enrollment.

• Patient received plasmapheresis within 4 weeks before enrollment.

• Patient had major surgery within 4 weeks before enrollment. (Kyphoplasty is not considered major surgery.)

• Patient has a history of allergic reaction attributable to compounds containing boron or mannitol.

• Patient has peripheral neuropathy of Grade 2 or greater intensity, as defined by the NCI Common Toxicity Criteria (NCI CTC):

• Grade 2: Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living (ADLs).

• Grade 3: Sensory loss or paresthesia interfering with ADLs.

• Grade 4: Permanent sensory loss that interferes with function.

• Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

• Patient was treated for a cancer other than multiple myeloma within 5 years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ.

• Patient has cardiac amyloidosis.

• Patient has poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.

• Patient is known to be human immunodeficiency virus (HIV)-positive. (Patients assessed by the investigator to be at risk for HIV infection should be tested in accordance with local regulations.)

• Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection.

• Patient has an active systemic infection requiring treatment.

• Female patient is pregnant or breast-feeding.

• Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

Study Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• bortezomib

Locations

Country	Name	City	State
Austria	Wilhelminenspital Wien, Abt. Fur Med. und Medizinische Onkologie	Wien
Belgium	ACZA, Campus Stuivenberg	Antwerpen
Belgium	CHU Erasme / ULB University, Hematology 7th Floor	Brussels
Belgium	Institut Jules Bordet, Unite Sterile	Bruxelles
Belgium	C.H. Notre Dame-Reine Fabiola	Charleroi
Belgium	UZ Gasthuisberg, Department of Hematology	Leuven
Belgium	AZ St. Jan, Dept. of Haematology	Rugge
Belgium	Cliniques Universitaires U.C.L de Mont Godinne, Hopital de Jour	Yvoir
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Health Sciences Center	London	Ontario
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Toronto General Research Institute, Princess Margaret Hospital	Toronto	Ontario
France	Hopital Antoine Beclere, Hopital de Jour de Medecine Interne	Clamart
France	Hospital Claude Huriez, Service des Maladies du Sang	Lile	Cedex
France	Nantes Hotel Dieu Hospital	Nantes	Cedex
France	Hopital Cochin, Service de Hematologie	Paris
France	Hopital Hotel Dieu, Service d'hematologie et oncologie medicale	Paris
France	Hopital Saint-Louis, Direction Financiere	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Hopital Purpan, Pavillon Dieulafoy, Service d'Hematologie Clinique	Toulouse	Cedex
France	Hopital de Brabois, Service Hematologie et Medecine Interne	Vandoeuvre
France	Institut Gustave-Roussy, Service d'Hematologie	Villejuif	Cedex
Germany	Universitatsklinikum Charite, Abt. Fuer Haematologie/Onkologie	Berlin
Germany	Medizinische Klinik und Poliklinik 1	Bonn
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	University of Erlangen-Nurenberg, Division of Hematology/Oncology	Erlangen
Germany	Freiburg University Medical Center, Dept. of Hemayology/Oncology	Freiburg
Germany	Medical University Clinic (Oncology/Haematology)	Hamburg
Germany	St. Marien Hospital, Klinik fur Hamatologie und Onkologie	Hamm
Germany	Universitatsklinikum Heidelberg, Abt. Fur Haematologie und Onkologie	Heidelberg
Germany	University of Essen Medical School, Dept. of Internal Medicine	Hufelandstr
Germany	Johannes Gutenberg-Universitat Mainz, III. Med Klinik und Poliknik	Mainz
Germany	Uniklinikum Muenster	Muenster
Germany	Eberhard-Karls Universitat, Medizinische Klinik	Tubingen
Ireland	Belfast City Hospital	Belfast
Israel	RAMBAM Medical Center, Department of Hematology and Bone	Haifa
Israel	Hadassah University Hospital	Jerusalem
Italy	Dipartmento Clinico esperimentale Di Oncologia et Ematolgia	Bergamo
Italy	Instituto di Ematologia e Oncologia Medica, Lorenzo e Ariosto Seragnoli	Bologna
Italy	Dipartimento di Biotecnologie Cellulari ed Ematologia	Roma
Italy	Azienda Ospedaliera, S. Giovanni Battista	Torino
Netherlands	Dept. of Clinical Hematology, Academic Medical Center	Amsterdam
Netherlands	Department of Hematology, Erasmus MC, 1a, Daniel Den Hoed	Rotterdam
Netherlands	Dept. Hematology, University Medical Centre	Utrecht
Spain	Hospital Clinico Universitario de Barcelona, Haematology Department	Barcelona
Spain	University Hospital of Salamanca	Salamanca
Sweden	Department of Haematology, Huddinge University Hospital M54	Stockholm
Sweden	Karolinska Hospital, Dept. of Hematology	Stockholm
United Kingdom	Department of Haematology, Queen Elizabeth Hospital	Birmingham
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Department of Haematology, ICSM, Hammersmith Hospital	London
United Kingdom	Department of Haematology, St. Bartholomew's Hospital	London
United Kingdom	Royal Marsden Hospital, Leukaemia and Myeloma Units	Sutton
United Kingdom	Adult Leukaemia Unit, Christie Hospital	Withington	Manchester
United States	Department of Internal Medicine, Univ. of Michigan Comp. Cancer Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Beth Israel Deaconess Medical Center, Kirstein Room 135	Boston	Massachusetts
United States	Dana-Farber Cancer Center	Boston	Massachusetts
United States	Tufts New England Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Trident Palmetto Hematology/Oncology	Charleston	South Carolina
United States	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina
United States	Northwestern University Medical School	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor Institute for Immunology Research	Dallas	Texas
United States	Texas Oncology at Medical City Dallas Hospital	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Hackensack University Medical Center, David Jurist Research Building	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Hematology/Oncology Associates, PA	Jacksonville	Florida
United States	Scripps Clinic	La Jolla	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Loyola University Medical Center: Cardinal Bernardin Cancer Center	Maywood,	Illinois
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	VA Medical Center, Sections of Hematology/Oncology	Minneapolis	Minnesota
United States	Division of Hematology/Stem Cell Transplant	Nashville	Tennessee
United States	Long Island Jewish Medical Center, Division of Hematology/Oncology	New Hyde Park	New York
United States	NY Presbyterian Hospital	New York	New York
United States	St. Vincent's Comprehensive Cancer Center, Research Department	New York	New York
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital, Dept. of Human Oncology	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Rochester General Hospital, Lipson Cancer Blood Center	Rochester	New York
United States	University of Rochester Medical Center, James P. Wilmot Cancer Center	Rochester	New York
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	LSU HC	Shreveport	Louisiana
United States	Washington University School of Medicine	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center, University of S. Florida	Tampa	Florida
United States	Kaiser Permanente Oncology Clinical Trials	Vallejo	California
United States	Lombardi Cancer Center, Georgetown University Medical Center	Washington	District of Columbia
United States	Med Star Institute, Washington Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom,