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

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00048230

Collaborator

(none)

620

Enrollment

Locations

Duration (Months)

6.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: bortezomib	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

620 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Jul 1, 2004

Actual Study Completion Date :

Dec 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alta Bates Comprehensive Cancer Center	Berkeley	California	United States	94704
2	City of Hope	Duarte	California	United States	91010
3	Scripps Clinic	La Jolla	California	United States	92307
4	Loma Linda University Medical Center	Loma Linda	California	United States	92354
5	Kaiser Permanente Oncology Clinical Trials	Vallejo	California	United States	94589
6	Lombardi Cancer Center, Georgetown University Medical Center	Washington	District of Columbia	United States	20007
7	Med Star Institute, Washington Cancer Center	Washington	District of Columbia	United States	20010
8	Hematology/Oncology Associates, PA	Jacksonville	Florida	United States	32207
9	University of Miami	Miami	Florida	United States	33136
10	H. Lee Moffitt Cancer Center, University of S. Florida	Tampa	Florida	United States	33612
11	Emory University	Atlanta	Georgia	United States	30322
12	Northwestern University Medical School	Chicago	Illinois	United States	60611
13	Loyola University Medical Center: Cardinal Bernardin Cancer Center	Maywood,	Illinois	United States	60153
14	LSU HC	Shreveport	Louisiana	United States	71130
15	Tufts New England Medical Center	Boston	Massachusetts	United States	02111
16	Dana-Farber Cancer Center	Boston	Massachusetts	United States	02115
17	Beth Israel Deaconess Medical Center, Kirstein Room 135	Boston	Massachusetts	United States	02215
18	Department of Internal Medicine, Univ. of Michigan Comp. Cancer Center	Ann Arbor	Michigan	United States	48109-0922
19	VA Medical Center, Sections of Hematology/Oncology	Minneapolis	Minnesota	United States	55417
20	Mayo Clinic	Rochester	Minnesota	United States	55905
21	Washington University School of Medicine	St. Louis	Missouri	United States	63110
22	Hackensack University Medical Center, David Jurist Research Building	Hackensack	New Jersey	United States	07601
23	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
24	Long Island Jewish Medical Center, Division of Hematology/Oncology	New Hyde Park	New York	United States	11040
25	St. Vincent's Comprehensive Cancer Center, Research Department	New York	New York	United States	10011
26	NY Presbyterian Hospital	New York	New York	United States	10021
27	Rochester General Hospital, Lipson Cancer Blood Center	Rochester	New York	United States	14621
28	University of Rochester Medical Center, James P. Wilmot Cancer Center	Rochester	New York	United States	14642
29	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina	United States	28203
30	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
31	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
32	Western Pennsylvania Hospital, Dept. of Human Oncology	Pittsburgh	Pennsylvania	United States	15224
33	Trident Palmetto Hematology/Oncology	Charleston	South Carolina	United States	29406
34	Division of Hematology/Stem Cell Transplant	Nashville	Tennessee	United States	37232-5505
35	Texas Oncology at Medical City Dallas Hospital	Dallas	Texas	United States	75225
36	Baylor Institute for Immunology Research	Dallas	Texas	United States	75246
37	MD Anderson Cancer Center	Houston	Texas	United States	77030
38	Fred Hutchinson Cancer Center	Seattle	Washington	United States	98109
39	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
40	Wilhelminenspital Wien, Abt. Fur Med. und Medizinische Onkologie	Wien		Austria	1171
41	ACZA, Campus Stuivenberg	Antwerpen		Belgium	2060
42	CHU Erasme / ULB University, Hematology 7th Floor	Brussels		Belgium	1070
43	Institut Jules Bordet, Unite Sterile	Bruxelles		Belgium	1000
44	C.H. Notre Dame-Reine Fabiola	Charleroi		Belgium	6000
45	UZ Gasthuisberg, Department of Hematology	Leuven		Belgium	3000
46	AZ St. Jan, Dept. of Haematology	Rugge		Belgium	8000
47	Cliniques Universitaires U.C.L de Mont Godinne, Hopital de Jour	Yvoir		Belgium	5530
48	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
49	London Health Sciences Center	London	Ontario	Canada	N6A 4G5
50	Toronto General Research Institute, Princess Margaret Hospital	Toronto	Ontario	Canada	M5G2M9
51	Royal Victoria Hospital	Montreal	Quebec	Canada	H2W 1S6
52	Hospital Claude Huriez, Service des Maladies du Sang	Lile	Cedex	France	59037
53	Nantes Hotel Dieu Hospital	Nantes	Cedex	France	01 44093
54	Hopital Purpan, Pavillon Dieulafoy, Service d'Hematologie Clinique	Toulouse	Cedex	France	31059
55	Institut Gustave-Roussy, Service d'Hematologie	Villejuif	Cedex	France	94805
56	Hopital Antoine Beclere, Hopital de Jour de Medecine Interne	Clamart		France	92140
57	Hopital Hotel Dieu, Service d'hematologie et oncologie medicale	Paris		France	75004
58	Hopital Saint-Louis, Direction Financiere	Paris		France	75010
59	Hopital Cochin, Service de Hematologie	Paris		France	75014
60	Centre Hospitalier Lyon Sud	Pierre Benite Cedex		France	69495
61	Hopital de Brabois, Service Hematologie et Medecine Interne	Vandoeuvre		France	54511
62	Universitatsklinikum Charite, Abt. Fuer Haematologie/Onkologie	Berlin		Germany	10098
63	Medizinische Klinik und Poliklinik 1	Bonn		Germany	53127
64	Universitatsklinikum Carl Gustav Carus	Dresden		Germany	01307
65	University of Erlangen-Nurenberg, Division of Hematology/Oncology	Erlangen		Germany	91054
66	Freiburg University Medical Center, Dept. of Hemayology/Oncology	Freiburg		Germany	79106
67	Medical University Clinic (Oncology/Haematology)	Hamburg		Germany	20246
68	St. Marien Hospital, Klinik fur Hamatologie und Onkologie	Hamm		Germany	59071
69	Universitatsklinikum Heidelberg, Abt. Fur Haematologie und Onkologie	Heidelberg		Germany	69115
70	University of Essen Medical School, Dept. of Internal Medicine	Hufelandstr		Germany	55 45122
71	Johannes Gutenberg-Universitat Mainz, III. Med Klinik und Poliknik	Mainz		Germany	55101
72	Uniklinikum Muenster	Muenster		Germany	48129
73	Eberhard-Karls Universitat, Medizinische Klinik	Tubingen		Germany	72076
74	Belfast City Hospital	Belfast		Ireland	BT9 7AB
75	RAMBAM Medical Center, Department of Hematology and Bone	Haifa		Israel	31096
76	Hadassah University Hospital	Jerusalem		Israel	91120
77	Dipartmento Clinico esperimentale Di Oncologia et Ematolgia	Bergamo		Italy	24128
78	Instituto di Ematologia e Oncologia Medica, Lorenzo e Ariosto Seragnoli	Bologna		Italy	40138
79	Dipartimento di Biotecnologie Cellulari ed Ematologia	Roma		Italy	00161
80	Azienda Ospedaliera, S. Giovanni Battista	Torino		Italy	10126
81	Dept. of Clinical Hematology, Academic Medical Center	Amsterdam		Netherlands	1105
82	Department of Hematology, Erasmus MC, 1a, Daniel Den Hoed	Rotterdam		Netherlands	3075
83	Dept. Hematology, University Medical Centre	Utrecht		Netherlands	3584 CX
84	Hospital Clinico Universitario de Barcelona, Haematology Department	Barcelona		Spain	08036
85	University Hospital of Salamanca	Salamanca		Spain	37007
86	Department of Haematology, Huddinge University Hospital M54	Stockholm		Sweden	14186
87	Karolinska Hospital, Dept. of Hematology	Stockholm		Sweden	17176
88	Adult Leukaemia Unit, Christie Hospital	Withington	Manchester	United Kingdom	M20 4BX
89	Department of Haematology, Queen Elizabeth Hospital	Birmingham		United Kingdom	B15 2TH
90	Leeds General Infirmary	Leeds		United Kingdom	LS1 3EX
91	Department of Haematology, St. Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
92	Department of Haematology, ICSM, Hammersmith Hospital	London		United Kingdom	W12 0NN
93	Royal Marsden Hospital, Leukaemia and Myeloma Units	Sutton		United Kingdom	SM2 5PT