A Phase 3 Study Comparing Oral IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01564537
First received: March 22, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of this phase 3, randomized, double-blind, multicenter study is to compare Oral IXAZOMIB plus Lenalidomide and Dexamethasone versus Placebo plus Lenalidomide and Dexamethasone in adult patients with relapsed and/or refractory multiple myeloma.


Condition Intervention Phase
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Drug: IXAZOMIB + Lenalidomide + Dexamethasone
Drug: Placebo + Lenalidomide + Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral IXAZOMIB (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Change from the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    To determine whether the addition of oral IXAZOMIB to the background therapy of lenalidomide and dexamethasone improves PFS in patients with relapsed and/or refractory multiple myeloma


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ] [ Designated as safety issue: No ]
    To determine whether the addition of oral IXAZOMIB to lenalidomide and dexamethasone improves OS

  • Overall Response Rate (ORR), including Partial Response (PR), Very Good Partial Response (VGPR), and Complete Response (CR) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    Standard multiple myeloma disease assessments

  • CR + VGPR [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
    Standard multiple myeloma disease assessments

  • Duration of Response (DOR) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Time to Progression (TTP) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Number of AEs, SAEs, assessment of clinical laboratory values and evaluate Eastern Cooperative Group (ECOG) performance scores [ Time Frame: From the date of signing of the informed consent form through 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
    To determine the safety of addition of IXAZOMIB to lenalidomide and dexamethasone

  • Pain response rate as assessed by the BFI-SF and analgesic use [ Time Frame: BPI-SF will be assessed at screening; Day 1 of each cycle; at EOT and thereafter every 4 weeks until disease progression ] [ Designated as safety issue: No ]
  • Change in global health status, as measured by the patient reported outcome questionnaires, EORTC QLQ-C30 and MY-20 [ Time Frame: At the time of screening, Day 1 of Cycle 1 and Cycle 2; every other cycle until EOT; every 4 weeks after EOT until disease progression and thereafter every 12 weeks until OS ] [ Designated as safety issue: No ]
  • OS and PFS in high-risk population such as those carrying del(13), del(17), +1q21, t(4;14), or t(14;16) [ Time Frame: At the time of screening; Day 1 of each cycle; at EOT; every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination ] [ Designated as safety issue: Yes ]
  • To collect PK data including Cmax, AUC and Tmax to contribute to population PK analyses [ Time Frame: Days 1 & 14 of cycles 1&2. Day 1 of cycles 3-10 ] [ Designated as safety issue: No ]

Estimated Enrollment: 703
Study Start Date: August 2012
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IXAZOMIB
IXAZOMIB + Lenalidomide + Dexamethasone
Drug: IXAZOMIB + Lenalidomide + Dexamethasone
Patients will receive single oral dose of IXAZOMIB (4.0mg) on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days until disease progression
Placebo Comparator: Placebo
Placebo + Lenalidomide + Dexamethasone
Drug: Placebo + Lenalidomide + Dexamethasone
Patients will receive single oral dose of Placebo on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days until disease progression

  Eligibility

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

Inclusion Criteria:

  • Male or female patients 18 years or older
  • Diagnosed Multiple Myeloma according to standard criteria
  • Measurable disease as specified in study protocol
  • Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2
  • Patients with relapsed and/or refractory Multiple Myeloma who have received 1 to 3 prior therapies
  • Meet the clinical laboratories criteria as specified in the protocol
  • Patients who received prior allogenic transplant must have no active graft-versus-host disease (GVHD)
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse AND must adhere to the guidelines of the lenalidomide pregnancy prevention program
  • Must be able to take concurrent aspirin 325 mg daily
  • Voluntary written consent

Exclusion Criteria:

  • Patient who were refractory to lenalidomide or proteasome inhibitor-based therapy
  • Female patients who are lactating or pregnant
  • Major surgery or radiotherapy within 14 days before randomization
  • Infection requiring systematic antibiotics within 14 days before the first dose of study drug
  • Central nervous system involvement
  • Failure to have fully recovered from the effects of prior chemotherapy regardless of the interval since last treatment
  • Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before the first dose of study treatment
  • Diagnosis of Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
  • Evidence of current uncontrolled cardiovascular conditions
  • Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
  • Known allergy to any of the study medications
  • Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
  • Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive
  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: NCT01564537

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

  Hide Study Locations
Locations
United States, Alabama
Clearview Cancer Institute Withdrawn
Huntsville, Alabama, United States, 35805
United States, Arizona
Arizona Oncology Associates Withdrawn
Phoenix, Arizona, United States, 85016
United States, Arkansas
University of Arkansas Medical Sciences Withdrawn
Little Rock, Arkansas, United States, 72205
United States, California
Pacific Cancer Medical Center Incorporated Recruiting
Anaheim, California, United States, 92801
Alta Bates Comprehensive Cancer Center Recruiting
San Pablo, California, United States, 94806
United States, Florida
Shands Hospital at University of Florida Recruiting
Gainesville, Florida, United States, 32610
Cancer Care of North Florida Withdrawn
Lake City, Florida, United States, 32024
Cancer and Blood Disease Center Recruiting
Lecanto, Florida, United States, 34461
United States, Georgia
Northwest Georgia Oncology Center Recruiting
Marietta, Georgia, United States, 30060
United States, Illinois
John H. Stroger Jr. Hospital of Cook County Recruiting
Chicago, Illinois, United States, 60612
United States, Kentucky
Kentucky Cancer Clinic Withdrawn
Hazard, Kentucky, United States, 41701
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Withdrawn
Ann Arbor, Michigan, United States, 48109-5936
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, New Hampshire
Dartmouth Hitchcock Medical Center Withdrawn
Lebanon, New Hampshire, United States
Portsmouth Regional Hospital Withdrawn
Portsmouth, New Hampshire, United States, 03801
United States, New Jersey
Hackensack University Medical Center Withdrawn
Hackensack, New Jersey, United States, 17601
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Columbia University Medical Center Withdrawn
New York, New York, United States, 10032
Weill Medical College of Cornell University Withdrawn
New York, New York, United States, 10021
United States, North Carolina
Blood and Cancer Clinic Terminated
Fayetteville, North Carolina, United States, 28303
United States, Pennsylvania
Scranton Hematology Oncology Recruiting
Scranton, Pennsylvania, United States, 18510
United States, South Carolina
MUSC Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
United States, Tennessee
Jones Clinic Withdrawn
Germantown, Tennessee, United States, 38138
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
United States, Washington
Fred Hutchinson Cancer Research Recruiting
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Australia
Royal Adelaide Hospital Withdrawn
Adelaide SA, Australia, 5000
Austin Hospital Recruiting
Heidleberg, VIC, Australia, 3084
The Alfred Hospital Recruiting
Melbourne, VIC, Australia, 3004
The Prince of Wales Hospital Withdrawn
Randwick, NSW, Australia, 2031
Princess Alexandra Hospital Recruiting
Woolloongabba, Australia
Austria
Medizinische Universität Graz Recruiting
Graz, Austria, 8036
Universitätsklinikum Innsbruck Withdrawn
Innsbruck, Austria, 6020
Salzburger Landeskliniken Recruiting
Salzburg, Austria, 5020
Klinikum Wels-Grieskirchen GmbH Recruiting
Wels, Austria, 4600
Belgium
ZNA AZ Stuivenberg Recruiting
Andtwerpen, Belgium, 2060
UCL Saint Luc Recruiting
Brussels, Belgium, 1200
UZ Brussels Recruiting
Brussels, Belgium, 1090
CHU Ambroise Pare Recruiting
Mons, Belgium, 7000
H.-Hartziekenhuis Roeselare-Menen Recruiting
Roeselare, Belgium, 8800
Cliniques Universitaires UCL de Mont-Godinne Recruiting
Yvoir, Belgium, 5530
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada, T2N 2T9
Cross Cancer Centre Recruiting
Edmonton, Alberta, Canada, T6G-2G3
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, New Brunswick
Saint John Regional Hospital Recruiting
Saint John, New Brunswick, Canada, E2L 4L
Canada, Quebec
Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Canada
Hopital Notre-Dame du CHUM Withdrawn
Montreal, Canada
General Hospital Recruiting
St. John's, NL, Canada, A1B 3V6
Czech Republic
Fakultni nemocnice Ostrava Recruiting
Brno, Czech Republic, 625 00
Fakultni nemocnice Brno Recruiting
Brno, Czech Republic, 625 00
Fakultni nemocnice Hradec Kralove Recruiting
Hradec Kralove, Czech Republic, 500 05
Fakultni Nemocnice Olomouc Recruiting
Olomouc, Czech Republic, 775 00
Fakultni Nemocnice Kralovske Vinohrady Recruiting
Praha 10, Czech Republic, 100 34
Denmark
Aalborg Sygehus Recruiting
Aalborg, Denmark, 9100
Århus Universitetshospital, Århus Sygehus Recruiting
Aarhus C, Denmark, DK-8000
Rigshospitalet Recruiting
Kobenhavn O, Denmark, DK-2100
France
Hôpital Claude Huriez Recruiting
Lille Cedex, France, 59037
Hopital Universitaire Dupuytren Recruiting
Limoges Cedex, France, 87042
Institut Paoli Calmettes Recruiting
Marseille Cedex, France, 13273
Hôpital Saint Eloi Recruiting
Montpellier cedex 5, France, 34295
Hôtel-Dieu Recruiting
Nantes, France, 44000
Hôpital Saint Antoine Recruiting
Paris, France, 75012
Hopital Saint Louis Recruiting
Paris, France, 75010
Hôpitaux du Haut Leveque Recruiting
Pessac, France, 33604
Hôpital Pontchaillou 2 Rue Henri le Guilloux Recruiting
Rennes cedex 9, France, 35033
Hopital Purpan Recruiting
Toulouse, France, 31059
Hôpital Bretonneau Recruiting
Tours cedex, France, 37004
Germany
Helios Klinikum Bad Saarow Withdrawn
Bad Saarow, Germany
Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, D-12200
Universitätsklinikum Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Krankenhaus Nordwest Withdrawn
Frankfurt am Main, Germany, 60488
Universität Greifswald Withdrawn
Greifswald, Germany, 17475
Asklepios Klinik Altona Recruiting
Hamburg, Germany, 22763
Hämatologische / Onkologische Praxisgemeinschaft Recruiting
Munchen, Germany, 81242
Universitätsklinikum Ulm Recruiting
Ulm, Germany, 89081
Hungary
Egyesitett Szent Istvan es Szent Laszlo Korhaz Recruiting
Budapest, Hungary, 1097
Debreceni Egyetem Orvos- és Egészségtudományi Cent Recruiting
Debrecen, Hungary, 4032
Pándy Kálmán Megyei Kórház Recruiting
Gyula, Hungary, 5700
Israel
Rambam Medical Center Active, not recruiting
Haifa, Israel, 31096
Rambam Medical Center Recruiting
Haifa, Israel, 31096
Hadassah University Hospital Ein Kerem Active, not recruiting
Jerusalem, Israel, 91120
Hadassah University Hospital Ein Kerem Recruiting
Jerusalem, Israel, 91120
Meir Medical Center Active, not recruiting
Kfar Saba, Israel, 44281
Meir Medical Center Recruiting
Kfar Saba, Israel, 44281
Western Galilee Hospital - Nahariya Active, not recruiting
Nahariya, Israel, 22100
Western Galilee Hospital Nahariya Recruiting
Nahariya, Israel, 22100
Rabin Medical Center Recruiting
Petach Tikva, Israel
Kaplan Medical Center Recruiting
Rehovot, Israel, 76100
Kaplan Medical Center Active, not recruiting
Rehovot, Israel, 76100
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Tel Aviv Sourasky Medical Center Active, not recruiting
Tel Aviv, Israel, 64329
Italy
Azienda Ospedaliero-Universitaria di Bologna - Pol Recruiting
Bologna, Italy, 40138
Azienda Ospedaliera Universitaria Careggi Active, not recruiting
Fierenze, Italy, 50134
Azienda Ospedaliera Universitaria Careggi Recruiting
Firenze, Italy, 50134
IRST- Istituto Scientifico Romagnolo per Recruiting
Meldola, Italy
AORN Recruiting
Naples, Italy, 80131
Azienda Ospedaliero Universitaria di Parma Recruiting
Parma, Italy, 43126
Ospedale S. Eugenio Recruiting
Rome, Italy, 10-00144
Azienda Ospedaliera S. Maria di Terni Recruiting
Terni, Italy, 05100
A.S.O. Molinette S. Giovanni Battista Recruiting
Turin, Italy, 10126
Netherlands
AMC Recruiting
Amsterdam, Netherlands
VU Medisch Centrum Recruiting
Amsterdam, Netherlands
Universitair Medisch Centrum Groningen Recruiting
Groningen, Netherlands
Academisch Ziekenhuis Maastricht Recruiting
Maastricht, Netherlands
Erasmus MC (Central Location) Recruiting
Rotterdam, Netherlands
UMC Utrecht Recruiting
Utrecht, Netherlands
New Zealand
Middlemore Hospital Recruiting
Auckland, New Zealand, 1640
Canterbury Health Laboratories Recruiting
Christchurch, New Zealand, 8011
Auckland City Hospital Recruiting
Grafton Auckland, New Zealand, 1023
Waikato Hospital Recruiting
Hamilton, New Zealand, 3240
Palmerston North Hospital Recruiting
Palmerston North, New Zealand, 4414
Wellington Regional Hospital Recruiting
Wellington, New Zealand, 6021
Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Recruiting
Chorzow, Poland
Universitätsklinikum Ulm Recruiting
Gdansk, Poland, 80-952
Wojewodzki Szpital Specjalistyczny im. M. Kopernik Recruiting
Lodz, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 Recruiting
Lublin, Poland
Portugal
Hospital de Braga Recruiting
Braga, Portugal
Centro Hospitalar e Universitário de Coimbra, EPE Recruiting
Coimbra, Portugal, 3000-075
Instituto Portugues de Oncologia do Porto Francisc Recruiting
Porto, Portugal, 4200-072
Romania
Emergency County Clinical Hospital Brasov Recruiting
Brasov, Romania, 500326
"Coltea" Clinical Hospital Recruiting
Bucharest, Romania, 30171
Emergency University Hospital Recruiting
Bucharest, Romania, 050098
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore
National University Hospital Recruiting
Singapore, Singapore
Spain
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Hospital General Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28007
Hospital Costa del Sol Recruiting
Marbella, Spain, 29603
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Hospital Donostia Recruiting
San Sebastian, Spain, 20014
Hospital Universitario Miguel Servet Withdrawn
Zaragoza, Spain, 50009
Sweden
Sahlgrenska Universitetssjukhuset Recruiting
Goteborg, Sweden, SE-413 45
Skånes Universitetssjukhus- Lund Recruiting
Lund, Sweden, SE-221- 85
Karolinska universitetssjukhuset Solna Recruiting
Stockholm, Sweden, SE-14186
Karolinska Universitetssjukhuset i Huddinge Recruiting
Stockholm, Sweden, SE-14186
Turkey
Ankara University Medical Faculty Cebeci Hospital Recruiting
Ankara, Turkey
Gazi University Medical Faculty Recruiting
Ankara, Turkey
Erciyes University Medical Faculty Recruiting
Kayseri, Turkey
United Kingdom
Aberdeen Royal Infirmary Recruiting
Aberdeen, United Kingdom, AB2 2ZN
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Ninewells Hospital Recruiting
Dundee, United Kingdom, DD1 9SY
Christie Hospital NHS Foundation Trust Recruiting
Manchester, United Kingdom
Southampton General Hospital Recruiting
Southampton, United Kingdom, SO16 6YD
The Royal Wolverhampton Hospitals NHS Trust Recruiting
Wolverhampton, United Kingdom, WV10 0QP
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01564537     History of Changes
Other Study ID Numbers: C16010, 2011-005496-17, CTR20130908
Study First Received: March 22, 2012
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Millennium Pharmaceuticals, Inc.:
Relapsed multiple myeloma
Refractory multiple myeloma
IXAZOMIB
MLN9708
Proteasome inhibitor
Tourmaline-MM1

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014