- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02969837
Study of Initial Treatment With Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in Multiple Myeloma
Open-label, Single-arm, Phase 2 Study of Initial Treatment With Elotuzumab, Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (E-KRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary Objective
• The primary efficacy endpoint will be the rate of sCR and/or the rate of negative MRD by next generation gene sequencing (NGS) by clonoSIGHT (Adaptive Biotechnologies) at the end of 8 cycles among non-transplant candidates and transplant candidates who agreed to defer transplant
Secondary Objectives
- To evaluate the safety and tolerability of elotuzumab in combination with KRd, when administered to subjects with newly diagnosed multiple myeloma.
- To determine the rate of MRD by next generation gene sequencing (NGS) by clonoSIGHT (Adaptive Biotechnologies) and by multi-color flow cytometry (MFC) at the end of Cycle 4, 8,and 12 for all subjects, and end of C18 (for subjects who are MRD+ at the end of C8 but MRD- at the end of C12 only), 24 months after C1D1, and yearly after that.
- To estimate time to event, including duration of response (DOR), progression-free survival (PFS), time to progression (TTP), and overall survival (OS).
Exploratory Objectives
- GEP, proteomics, and gene sequencing to evaluate the correlation between treatment outcome and pre-treatment subject profile.
- Immunologic correlative studies including FcγRIIIa V genotype.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago
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Evanston, Illinois, United States, 60201
- NorthShore University Health System
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible to enroll in this study. No enrollment waivers will be granted.
Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy
a. Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids and/or lenalidomide and/or bortezomib/PI-based regimens does not disqualify the subject (the corticosteroid treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle of lenalidomide and/or PI-based therapy)
- Both transplant and non-transplant candidates are eligible.
- Diagnosis of symptomatic multiple myeloma as per current IMWG uniform criteria prior to initial treatment
- Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma
Measurable disease, prior to initial treatment as indicated by one or more of the following:
- Serum M-protein ≥ 1 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable (≥ 1 g/dL)
- Involved serum free light chains ≥ 10 mg/dL provided that free light chain ratio is abnormal
Screening laboratory values must meet the following criteria and should be obtained within 21 days prior to enrollment WBC ≥ 2000/µL Platelets ≥ 75 x103/µL ANC >1000/µL Hemoglobin > 8.0 g/dL Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 50 mL/min
Use the Cockcroft-Gault formula below):
o Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
o Male CrCl = (140 - age in years) x weight in kg x 1.00
- 72 x serum creatinine in mg/dL
- Alternatively to Cockcroft-Gault formula of CrCl, 24hr urine CrCl can be used AST/ALT ≤ 3 x ULN Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) or ≤ 2 x ULN if lenalidomide is being prescribed.
- Males and females ≥ 18 years of age
- ECOG performance status of 0-1
- Females of childbearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide. The first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before lenalidomide is prescribed for Cycle 1 (prescriptions must be filled within 7 days).
- FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
- All study participants in the US must be consented to and registered into the mandatory Revlimid REMS program and be willing and able to comply with the requirements of Revlimid REMS.
- Voluntary written informed consent
Exclusion Criteria:
Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study. No enrollment waivers will be granted.
- Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, and no measurable disease as per IMWG by Freelite.
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Geriatric assessment score of ≥2 as defined by Palumbo et al.
- Known or suspected Amyloidosis
- Plasma cell leukemia
- Within 4 weeks since any plasmapheresis
- Within 3 weeks of any corticosteroids except per inclusion criteria #2
- Waldenström's macroglobulinemia or IgM myeloma
- Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater
- Subjects not able to tolerate elotuzumab, lenalidomide, carfilzomib, or dexamethasone
- Peripheral neuropathy ≥ Grade 2 at screening
- Prior CVA with persistent neurological deficit
- Diarrhea > Grade 1 in the absence of antidiarrheals
- CNS involvement
- Corrected calcium ≥ 11.5 mg/dL within 2 weeks of randomization
- Pregnant or lactating females
- Radiotherapy within 14 days before randomization. Seven days may be considered if to single area
- Major surgery within 3 weeks prior to first dose
Subject has clinically significant cardiac disease, including:
- myocardial infarction within 1 year before Cycle 1 Day 1, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV
- uncontrolled cardiac arrhythmia (NCI CTCAE Version 4 Grade 2:2) or clinically significant ECG abnormalities
- screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
- Uncontrolled HTN 14 days prior to enrollment
- Prior or concurrent deep vein thrombosis or pulmonary embolism
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
- Uncontrolled hypertension (defined as average systolic blood pressure ≥140 or average diastolic blood pressure ≥90, with blood pressure measured ≥3 times in the two weeks prior to enrollment ) or diabetes
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Active infection
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who are seropositive because of hepatitis B virus vaccine are eligible.
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
- Any clinically significant medical disease or condition that, in the Treating Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: E-KRd regimen
Participants will receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone.
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Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15
Other Names:
Carfilzomib will be given on Day 1 and 8 of Cycle 1, Days 1, 8, and 15 of Cycles 2-8, and Days 1 and 15 of Cycles 9 and beyond
Other Names:
Lenalidomide will be given on days 1-21 for all cycles.
Other Names:
Dexamethasone will be given as follows: Cycle 1 and 2: Days 1, 2, 8, 9, 15, 16, and 22 Cycles 3 and Beyond: Days 1, 8, 15, and 22 |
Experimental: E-Rd Regimen
Participants will receive elotuzumab, lenalidomide, and dexamethasone.
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Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15
Other Names:
Lenalidomide will be given on days 1-21 for all cycles.
Other Names:
Dexamethasone will be given as follows: Cycle 1 and 2: Days 1, 2, 8, 9, 15, 16, and 22 Cycles 3 and Beyond: Days 1, 8, 15, and 22 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Rate of sCR
Time Frame: At the end of eight months
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At the end of eight months
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Rate of negative MRD
Time Frame: At the end of eight months
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At the end of eight months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events of elotuzumab in combination with KRd
Time Frame: Through study completion an average of one year, adverse events will be monitored in real time
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Adverse events will be monitored in real time and discussed at a weekly data and safety monitoring conference.
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Through study completion an average of one year, adverse events will be monitored in real time
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Rate of MRD
Time Frame: At the end of four, eight, and twelve months for certain subjects.
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At the end of four, eight, and twelve months for certain subjects.
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Duration of response
Time Frame: Through study completion an average of one year
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These events will be analyzed at differing points of time based on the individual subjects disease progression.
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Through study completion an average of one year
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Progression free survival
Time Frame: Through study completion an average of one year
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These events will be analyzed at differing points of time based on the individual subjects disease progression.
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Through study completion an average of one year
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Time to progression
Time Frame: Through study completion an average of one year
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These events will be analyzed at differing points of time based on the individual subjects disease progression.
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Through study completion an average of one year
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Overall survival
Time Frame: Through study completion an average of one year
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These events will be analyzed at differing points of time based on the individual subjects disease progression.
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Through study completion an average of one year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Logisitc Regression for analyzing exploratory biomarkers
Time Frame: After study completion an average of one year
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Subjects will have the option to participate in additional genetic components of this trial if they provide their consent.
Once a subject has completed participation in the trial, if they agree to participate in the optional components their disease will be analyzed in relation to people with similar genetic make up.
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After study completion an average of one year
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andrzej Jakubowiak, MD, University of Chicago
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dexamethasone
- Lenalidomide
- Elotuzumab
Other Study ID Numbers
- IRB16-1138
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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