Overview

This trial is active, not recruiting.

Condition relapsed multiple myeloma
Treatments dexamethasone, lenalidomide, carfilzomib
Phase phase 3
Target proteasome
Sponsor Onyx Therapeutics, Inc.
Start date June 2010
End date June 2014
Trial size 780 participants
Trial identifier NCT01080391, PX-171-009

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Cycles 1 and higher (28 days each): lenalidomide and dexamethasone
dexamethasone
40 mg PO or IV on Days 1, 8, 15, 22
lenalidomide Revlimid
25 mg PO on Days 1-21
(Experimental)
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)
dexamethasone
40 mg PO or IV on Days 1, 8, 15, 22
lenalidomide Revlimid
25 mg PO on Days 1-21
carfilzomib PR-171
20 mg/m2, 27 mg/m2

Primary Outcomes

Measure
Progression-free survival (PFS)
time frame: 18 months

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator A. Keith Stewart, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.