Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma
Condition: Relapsed Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Lenalidomide; Carfilzomib
Intervention description: 40 mg orally or IV on days 1, 8, 15, 22; 25 mg orally on days 1-21; 20 mg/m², 27 mg/m² intravenously
Intervention MeSH terms: Dexamethasone; Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 792.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      The primary objective was to compare progression-free survival in adults with relapsed
      multiple myeloma who are receiving CRd vs participants receiving Rd in a randomized
      multicenter setting.
    

Eligibility 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 immunoglobulin A (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 (ECOG) performance status 0-2

          9. Adequate hepatic function, with serum alanine aminotransferase (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, New York Hear
             Association (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 myelodysplastic syndromes (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