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

Phase 3
18 Years
Open (Enrolling)
Relapsed Multiple Myeloma

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Trial Information

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

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.

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

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

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

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

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

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

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

20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Description:

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.

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

A. Keith Stewart, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA


Austria: Federal Ministry of Health

Study ID:




Start Date:

June 2010

Completion Date:

March 2014

Related Keywords:

  • Relapsed Multiple Myeloma
  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Mayo ClinicRochester, Minnesota  55905
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Cancer and Blood Disease CenterLecanto, Florida  34461
NYU Clinical Cancer CenterNew York, New York  10016
UT Southwestern Medical Center at DallasDallas, Texas  75390
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Kansas City Cancer Center, LLCOverland Park, Kansas  66210
Rocky Mountain Blood and Marrow Transplant ProgramDenver, Colorado  80218
Froedtert & Medical College of WisconsinMilwaukee, Wisconsin  53226
Redwood Regional Medical Group, IncSanta Rosa, California  94503
The University of Michigan - Comprehensive Cancer CenterAnn Arbor, Michigan  48109
Baylor University Medical Center, Blood & Marrow Transplant CenterDallas, Texas  75246
Scott and White Cancer Research InstituteTemple, Texas  76508