Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02969837
Previous Study | Return to List | Next Study

Study of Initial Treatment With Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02969837
Recruitment Status : Recruiting
First Posted : November 21, 2016
Last Update Posted : October 9, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Amgen
Multiple Myeloma Research Foundation
Information provided by (Responsible Party):
University of Chicago

Brief Summary:
This study will be a multi-center, open-label, Phase 2 study where newly diagnosed Multiple Myeloma requiring systemic chemotherapy will be eligible for enrollment. A total of 55 subjects will be enrolled. Time to progression or death will be calculated from the date of first treatment on protocol until the date of disease progression or death from any cause. Patients can expect to participate between 12-24 cycles. The primary endpoint will be the rate of response by next generation gene sequencing at the end of 8 cycles among non-transplant candidates and transplant candidates who agreed to defer transplant.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Elotuzumab Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

All participants will receive E-KRd regimen (elotuzumab, carfilzomib, lenalidomide, and dexamethasone) for up to 12 Cycles.

After Cycle 12, participants that are MRD negative will move to E-Rd (elotuzumab, carfilzomib, lenalidomide, and dexamethasone) maintenance regimen and continue until disease progression. Participants that are MRD positive will continue to receive E-KRd regimen for an additional 6 cycles followed by E-Rd maintenance regimen and continue until disease progression

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 10, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: E-KRd regimen
Participants will receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone.
Drug: Elotuzumab
Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15
Other Name: Empliciti

Drug: Carfilzomib
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 Name: Kryprolis

Drug: Lenalidomide
Lenalidomide will be given on days 1-21 for all cycles.
Other Name: Revlimid

Drug: Dexamethasone

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.
Drug: Elotuzumab
Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15
Other Name: Empliciti

Drug: Lenalidomide
Lenalidomide will be given on days 1-21 for all cycles.
Other Name: Revlimid

Drug: Dexamethasone

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





Primary Outcome Measures :
  1. Rate of sCR [ Time Frame: At the end of eight months ]
  2. Rate of negative MRD [ Time Frame: At the end of eight months ]

Secondary Outcome Measures :
  1. 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 ]
    Adverse events will be monitored in real time and discussed at a weekly data and safety monitoring conference.

  2. Rate of MRD [ Time Frame: At the end of four, eight, and twelve months for certain subjects. ]
  3. Duration of response [ Time Frame: Through study completion an average of one year ]
    These events will be analyzed at differing points of time based on the individual subjects disease progression.

  4. Progression free survival [ Time Frame: Through study completion an average of one year ]
    These events will be analyzed at differing points of time based on the individual subjects disease progression.

  5. Time to progression [ Time Frame: Through study completion an average of one year ]
    These events will be analyzed at differing points of time based on the individual subjects disease progression.

  6. Overall survival [ Time Frame: Through study completion an average of one year ]
    These events will be analyzed at differing points of time based on the individual subjects disease progression.


Other Outcome Measures:
  1. Logisitc Regression for analyzing exploratory biomarkers [ Time Frame: After study completion an average of one year ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

    1. 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)

    2. Both transplant and non-transplant candidates are eligible.
    3. Diagnosis of symptomatic multiple myeloma as per current IMWG uniform criteria prior to initial treatment
    4. Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma
    5. Measurable disease, prior to initial treatment as indicated by one or more of the following:

      1. Serum M-protein ≥ 1 g/dL
      2. Urine M-protein ≥ 200 mg/24 hours
      3. If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable (≥ 1 g/dL)
      4. Involved serum free light chains ≥ 10 mg/dL provided that free light chain ratio is abnormal
    6. 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

      1. 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
      2. 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.
    7. Males and females ≥ 18 years of age
    8. ECOG performance status of 0-1
    9. 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).
    10. 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.
    11. 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.
    12. 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.
    13. 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.

    1. 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.
    2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
    3. Geriatric assessment score of ≥2 as defined by Palumbo et al.
    4. Known or suspected Amyloidosis
    5. Plasma cell leukemia
    6. Within 4 weeks since any plasmapheresis
    7. Within 3 weeks of any corticosteroids except per inclusion criteria #2
    8. Waldenström's macroglobulinemia or IgM myeloma
    9. 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
    10. Subjects not able to tolerate elotuzumab, lenalidomide, carfilzomib, or dexamethasone
    11. Peripheral neuropathy ≥ Grade 2 at screening
    12. Prior CVA with persistent neurological deficit
    13. Diarrhea > Grade 1 in the absence of antidiarrheals
    14. CNS involvement
    15. Corrected calcium ≥ 11.5 mg/dL within 2 weeks of randomization
    16. Pregnant or lactating females
    17. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area
    18. Major surgery within 3 weeks prior to first dose
    19. 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
    20. Uncontrolled HTN 14 days prior to enrollment
    21. Prior or concurrent deep vein thrombosis or pulmonary embolism
    22. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
    23. 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
    24. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
    25. Active infection
    26. 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.
    27. 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
    28. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02969837


Contacts
Layout table for location contacts
Contact: Jennifer Nam 773-702-7716 jnam@medicine.bsd.uchicago.edu

Locations
Layout table for location information
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Jennifer Nam    773-702-7716    jnam@medicine.bsd.uchicago.edu   
NorthShore University Health System Not yet recruiting
Evanston, Illinois, United States, 60201
United States, Michigan
University of Michigan Comprehensive Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Chicago
Bristol-Myers Squibb
Amgen
Multiple Myeloma Research Foundation
Investigators
Layout table for investigator information
Principal Investigator: Andrzej Jakubowiak, MD University of Chicago

Layout table for additonal information
Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02969837     History of Changes
Other Study ID Numbers: IRB16-1138
First Posted: November 21, 2016    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Chicago:
Multiple Myeloma
Elotuzumab
Carfilzomib (Kyprolis)
Lenalidomide (Revlimid)
Dexamethasone (E-KRd)
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Lenalidomide
Elotuzumab
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents