Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma
Status: | Completed |
---|---|
Conditions: | Blood Cancer, Hematology |
Therapuetic Areas: | Hematology, Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 1/16/2019 |
Start Date: | July 14, 2010 |
End Date: | December 5, 2017 |
A Randomized, Multicenter, Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma
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.
multiple myeloma who are receiving CRd vs participants receiving Rd in a randomized
multicenter setting.
This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens
for adults 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). Participants will receive the treatment determined by randomization in 28-day
cycles until disease progression or unacceptable toxicity (whichever occurs first).
for adults 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). Participants will receive the treatment determined by randomization in 28-day
cycles until disease progression or unacceptable toxicity (whichever occurs first).
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
We found this trial at
23
sites
1100 Fairview Avenue North
Seattle, Washington 98109
Seattle, Washington 98109
(206) 667-5000
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
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1500 East Medical Center Drive
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
800-865-1125
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
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Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
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1721 East 19th Ave., Suite #200 & #300
Denver, Colorado 80218
Denver, Colorado 80218
720-754-4800
Colorado Blood Cancer Institute When patients come to the Colorado Blood Cancer Institute, the entire...
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92 2nd St
Hackensack, New Jersey 07601
Hackensack, New Jersey 07601
(201) 996-5900
John Theurer Cancer Center at the Hackensack University Medical Center The mission of the John...
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1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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9200 W Wisconsin Ave
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
(414) 805-3666
Froedtert and the Medical College of Wisconsin Froedtert Health combines with the Medical College of...
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Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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Scott & White Memorial Hospital When Arthur C. Scott, MD, and Raleigh R. White Jr.,...
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