Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. ) Identifier:
First received: March 2, 2010
Last updated: January 8, 2015
Last verified: January 2015

To compare progression-free survival in subjects with relapsed multiple myeloma who are receiving CRd vs subjects receiving Rd in a randomized multicenter setting.

Condition Intervention Phase
Relapsed Multiple Myeloma
Drug: Dexamethasone
Drug: Lenalidomide
Drug: Carfilzomib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The primary objective of this study is to compare PFS in subjects with relapsed multiple myeloma who are receiving CRd vs subjects receiving Rd alone in a randomized multicenter setting.

Secondary Outcome Measures:
  • Overall Survival, overall response rate, duration of response, disease control rate, safety, time to progression, change from baseline in quality of life assessment; QOL subscales of EORTC; time to next treatment; clinical benefit response [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Investigating the effect of carfilzomib given with lenalidomide and dexamethasone on other standard efficacy variables including ORR (sCR + CR + VGPR + PR), disease control rate (DCR), duration of response (DOR), OS, time to progression (TTP), and change from baseline in quality of life assessment. Additionally, this study will examine the safety profile of CRd compared with Rd alone based on the incidence and severity of AEs and laboratory changes.

Estimated Enrollment: 780
Study Start Date: June 2010
Estimated Study Completion Date: March 2017
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lenalidomide and Dexamethasone (Rd)
Cycles 1 and higher (28 days each): lenalidomide and dexamethasone
Drug: Dexamethasone
40 mg PO or IV on Days 1, 8, 15, 22
Drug: Lenalidomide
25 mg PO on Days 1-21
Other Name: Revlimid
Experimental: Carfilzomib, Lenalidomide, and Dexamethasone (CRd)

Cycles 1 through 12 (28 days each): carfilzomib (6 doses per cycle), lenalidomide, and dexamethasone

Cycles 13 through 18 (28 days each): carfilzomib (4 doses per cycle), lenalidomide, and dexamethasone

Cycles 19 and higher (28 days each): lenalidomide and dexamethasone (no carfilzomib)

Drug: Dexamethasone
40 mg PO or IV on Days 1, 8, 15, 22
Drug: Lenalidomide
25 mg PO on Days 1-21
Other Name: Revlimid
Drug: Carfilzomib
20 mg/m2, 27 mg/m2
Other Name: PR-171

Detailed Description:

This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens for subjects with relapsed multiple myeloma. Eligible subjects will be randomized in a 1:1 ratio to receive either the control Rd or CRd. Randomization will be stratified by β2 microglobulin levels (< vs ≥ 2.5 mg/L), prior bortezomib (no vs yes), and prior lenalidomide (no vs yes). Subjects will receive the treatment determined by randomization in 28-day cycles until disease progression or unacceptable toxicity (whichever occurs first). The primary endpoint of this Phase 3 study is progression-free survival.


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

Inclusion Criteria:

  1. Symptomatic multiple myeloma
  2. Measurable disease, as defined by one or more of the following (assessed within 21 days prior to randomization):

    • Serum M-protein ≥ 0.5 g/dL
    • Urine Bence-Jones protein ≥ 200 mg/24 hours
    • For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)
  3. Prior treatment with at least one, but no more than three, regimens for multiple myeloma
  4. Documented relapse or progressive disease on or after any regimen
  5. Achieved a response to at least one prior regimen
  6. Age ≥ 18 years
  7. Life expectancy ≥ 3 months
  8. Eastern Cooperative Oncology Group performance status 0-2
  9. Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 21 days prior to randomization
  10. Absolute neutrophil count ≥ 1.0 × 10^9/L within 21 days prior to randomization
  11. Hemoglobin ≥ 8 g/dL (80 g/L) within 21 days prior to randomization
  12. Platelet count ≥ 50 × 10^9/L (≥ 30 × 10^9/L if myeloma involvement in the bone marrow is > 50%) within 21 days prior to randomization
  13. Creatinine clearance (CrCl) ≥ 50 mL/minute within 21 days prior to randomization
  14. Written informed consent in accordance with federal, local, and institutional guidelines
  15. Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception
  16. Male subjects must agree to practice contraception

Exclusion Criteria:

  1. If previously treated with bortezomib (alone or in combination), progression during treatment
  2. If previously treated with a lenalidomide and dexamethasone (len/dex) combination:

    • Progression during the first 3 months of initiating treatment
    • Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
  3. Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded
  4. Prior carfilzomib treatment
  5. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  6. Waldenström's macroglobulinemia or IgM myeloma
  7. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
  8. Chemotherapy or investigational agent within 3 weeks prior to randomization or antibody therapy within 6 weeks prior to randomization
  9. Radiotherapy to multiple sites or immunotherapy/antibody therapy within 28 days prior to randomization; localized radiotherapy to a single site within 7 days prior to randomization
  10. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 21 days prior to randomization
  11. Pregnant or lactating females
  12. Major surgery within 21 days prior to randomization
  13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
  14. Known human immunodeficiency virus infection
  15. Active hepatitis B or C infection
  16. Myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
  17. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
  18. Other malignancy, including MDS, within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
  19. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization
  20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  22. Ongoing graft-vs-host disease
  23. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization
  24. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  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 identifier: NCT01080391

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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, California
Providence St. Joseph Medical Center
Burbank, California, United States, 91505
St. Jude Hospital Yorba Linda dba; St. Joseph Heritage Healthcare
Santa Rosa, California, United States, 94503
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Florida
Cancer and Blood Disease Center
Lecanto, Florida, United States, 34461
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66160
United States, Michigan
The University of Michigan - Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
NYU Clinical Cancer Center
New York, New York, United States, 10016
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Tennessee
Associates in Oncology and Hematology
Chattanooga, Tennessee, United States, 37404
United States, Texas
The Don & Sybil Harrington Cancer Center
Amarillo, Texas, United States, 79106
Baylor Sammons Cancer Center
Dallas, Texas, United States, 75246
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-8565
The University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
Scott and White Memorial Hospital
Temple, Texas, United States, 76508
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, Wisconsin
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Medizinische Universitat Wien
Wien, Austria, 1090
Wilhelminspital der Stadt Wien, Zentrum fur Onkologie und Hamatologie
Wien, Austria, 1171
Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg
Antwerpen, Belgium, 2060
AZ Sint-Jan AV
Brugge, Belgium, 8000
UZ Brussel
Brussels, Belgium, 1090
Cliniques Universitaires Saint-Luc
Bruxelles, Belgium, 1200
Institut Jules Bordet
Bruxelles, Belgium, 1000
UZ Leuven
Leuven, Belgium, 3000
University Multiprofile Hospital for Active Treatment, "Dr. Georgi Stranski"
Pleven, Bulgaria, 5800
University Multiprofile Hospital for Active Treatment "Sveti Georgi"
Plovdiv, Bulgaria, 4002
Specialized Hospital for Active Treatment of Hematological Diseases
Sofia, Bulgaria, 1756
Military Medical Academy Multiprofile Hospital for Active Treatment
Sofia, Bulgaria, 1606
Multiprofile Hospital for Active Treatment "Sveta Marina"
Varna, Bulgaria, 9010
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
University of Alberta, Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
Cancer Care Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Newfoundland and Labrador
General Hospital, Health Sciences Centre
St John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Sir Mortimer B. Davis - Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
McGill University Health Center, Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1
Czech Republic
University Hospital Brno, Department of Internal Medicine - Hematooncology
Brno, Czech Republic, 625 00
University Hospital Hradec Kralove
Hradec Kralove, Czech Republic, 500 05
University Hospital Olomouc
Olomouc, Czech Republic, 775 20
University Hospital Kralovske Vinohrady - Prague
Praha 10, Czech Republic, 100 34
General University Hospital Prague
Praha 2, Czech Republic, 128 08
Hospital Antoine Beclere
Clamart, France, 92140
Clinique Victor Hugo - Centre Jean Bernard
Le Mans, France, 72000
Hopital Claude Huriez
Lille, France, 59037
CH de Mulhouse, Hopital Emile Muller
Mulhouse, France, 68070
CHU Nantes Hotel Dieu
Nantes, France, 44093
Groupe Hospitalier Necker - Enfants Malades
Paris, France, 75015
Hopital Saint-Antoine
Paris, France, 75012
Cancer Institut Universitaire de Toulouse-Oncopole (iUCT)
Toulouse, France, 31100
Hopitaux de Brabois
Vandoeuvre-Les-Nancy, France, 54511
University of Dusseldorf
Dusseldorf, Germany, 40225
Krankenhaus Nordwest
Frankfurt am Main, Germany, 60488
University of Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitat Heidelberg
Heidelberg, Germany, 69120
Stiftungsklinikum Mittelrhein
Koblenz, Germany, 56068
LMU Klinikum der Universitat
Munchen, Germany, 81377
Universitatsklinikum Munster
Munster, Germany, 48129
Universitatsklinikum Wurzburg
Wurzburg, Germany, 97080
Alexandra Hospital
Athens, Greece, 11528
University General Hospital of Patras
Patras, Greece, 26500
St. Istvan and St. Laszlo Hospital of Budapest
Budapest, Hungary, H-1097
University of Debrecen, Medical and Health Science Center
Debrecen, Hungary, H-4032
Petz Aladar County Teaching Hospital
Gyor, Hungary, H-9032
Bekes County Pandy Kalman Hospital
Gyula, Hungary, H-5700
Kaposi Mor County Teaching Hospital
Kaposvar, Hungary, H-7400
University of Pecs
Pecs, Hungary, H-7624
University of Szeged, Albert Szent-Gyorgi Clinical Center
Szeged, Hungary, H-6720
Rambam Medical Center
Haifa, Israel, 31096
Hadassah Medical Center, Ein Kerem
Jerusalem, Israel, 91120
Western Gailee Hospital - Nahariya
Nahariya, Israel, 22100
Rabin Medical Center
Petach Tikva, Israel, 49100
The Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
Kaplan Medical Center
Rehovot, Israel, 76100
Azienda Ospedallera Niguarda Ca Granda
Milano, Italy, 20162
Azienda Ospedllero Maggiore della Carita
Novara, Italy, 28100
Azienda Ospedaliera Pisana Ospendale Santa Chiara - Main
Pisa, Italy, 56216
Ospedale S. Eugenio
Roma, Italy, 00144
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, Italy, 10126
Erasmus MC, Department of Haematology
Rotterdam, Netherlands, 3015 CE
University Clinical Centre, Department of Hematologii Transplantologii
Gdansk, Poland, 80-952
Samodzielny Publ. Szp. Wojewodzki w Gorzow Wlkp.
Gorzow Wielkopolski, Poland, 66-400
Independent Public Teaching Hospital of Medical University of Silesia in Katowice
Katowice, Poland, 40-027
Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz
Lodz, Poland, 93-510
Szpital Wojewwodzki im. dr Ludwika Rydygiera w Suwalkach
Suwalki, Poland, 16-400
Nicolaus Copernicus Municipal Specialist Hospital
Torun, Poland, 87-100
Maria Sklodowska-Curie Institute of Oncology
Warszawa, Poland, 02-781
Zamojski Non-Public Hospital
Zamosc, Poland, 22-400
Bucharest University Emergency Hospital
Bucharest, Romania, 050098
Coltea Clinical Hospital
Bucharest, Romania, 030-171
Fundeni Clinical Institute, "Stefan Berceanu" Center for Hematology and Bone Marrow Transplantation
Bucharest, Romania, 022328
Regional Institute of Iasi
Iasi, Romania, 700483
Russian Federation
State Medical Institution Komi Republican Oncological Center
Syktyvkar, Komi Republic, Russian Federation, 167904
First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia
Izhevsk, Russian Federation, 426039
Federal State Budget Institution: Hematology Research Center under MoH
Moscow, Russian Federation, 125167
Federal State Budgetary Scientific Institution: N.N. Blokhin Russian Cancer Research Center
Moscow, Russian Federation, 115478
Moscow State Medical Institution Municipal City Clinical Hospital n.a. S.P. Botkin
Moscow, Russian Federation, 125101
Federal State Budget Institute: Federal Almalov Medical Research Centre under Ministry of Healthcare
St. Petersburg, Russian Federation, 197341
FSBI: Russian Research Institute of Hematology and Blood Transfusion under the Ferderal Agency for M&B
St. Petersburg, Russian Federation, 191024
SHEI: First St. Petersburg State Medical University N.a.I.P Pavlov under MoH, Clinic of Bone Marrow Transplant
St. Petersburg, Russian Federation, 197101
State Higher Educational Institution: St Petersburg State Medical University n.a.I.P Pavlov
St. Petersburg, Russian Federation, 197022
Military Medical Academy, Clinic of Hematology
Belgrade, Serbia, 11000
Clinical Hospital Center Bezanijska Kosa
Belgrade, Serbia, 11000
Clinical Center of Serbia, Clinic of Hematology
Belgrade, Serbia, 11000
Clinical Center Nis, Clinic of Hematology
Nis, Serbia, 18 000
Clinical Center of Vojvodina, Clinic of Hematology
Novi Sad, Serbia, 21 000
Hospital Universitario Germans Trias i Pujol
Badalona, Spain, 08916
Hospital Clinic I Provincial
Barcelona, Spain, 08036
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Donostia
San Sebastian, Spain, 20014
Hospital Universitario y Politeecnico La Fe
Valencia, Spain, 46026
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Sahlgrenska Universitetssjukhuset
Goteborg, Sweden, SE-41345
Karolinska Universitetssjukhuset Solna, Hematologiskt Centrum
Stockholm, Sweden, SE-17176
Karolinska Universitetsjukhuset i Huddinge
Stockholm, Sweden, SE-14186
United Kingdom
Royal Free Hampstead
London, United Kingdom, NW3 2QG
St. Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
St. Georges Hospital
London, United Kingdom, SW17 0QT
Nottingham University Hospitals (City Campus)
Nottingham, United Kingdom, NG5 1PB
Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
The Royal Wolverhampton Hospital NHS Trust
Wolverhampton, United Kingdom, WV10 OQP
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Principal Investigator: A. Keith Stewart, MD Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA
Principal Investigator: S. Vincent Rajkumar, MD Division of Hematology and Internal medicine, Mayo Clinic, Rochester, Minnesota, USA
Principal Investigator: Philippe Moreau, MD Department of Hematology, University Hospital, Nantes, France
Principal Investigator: Antonio Palumbo, MD Divisione di Ematologia dell'Universita' di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
  More Information

No publications provided by Onyx Pharmaceuticals

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. ) Identifier: NCT01080391     History of Changes
Other Study ID Numbers: PX-171-009
Study First Received: March 2, 2010
Last Updated: January 8, 2015
Health Authority: Austria: Federal Ministry of Health
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Agence Française de Sécurité Sanitaire Produits de Santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organisation for Medicines
Hungary: National Institute for Pharmacy
Israel: Ministry of Health
Italy: Agencia Italiana del Farmaco
Netherlands: Medicines Evaluation Board
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Public Health Institue
Serbia: Medicines and Medical Devices Ageny of Serbia
Spain: Spanish Drug Agency
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Onyx Pharmaceuticals:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
BB 1101
Dexamethasone 21-phosphate
Dexamethasone acetate
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents processed this record on March 01, 2015