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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.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01080391
First received: March 2, 2010
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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: June 2016
Estimated Primary Completion Date: December 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.

  Eligibility

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

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 ClinicalTrials.gov identifier: NCT01080391

  Show 127 Study Locations
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
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

Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT01080391     History of Changes
Other Study ID Numbers: PX-171-009
Study First Received: March 2, 2010
Last Updated: December 20, 2013
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
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 25, 2014