Clinical Trials /

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

NCT02969837

Description:

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.

Related Conditions:
  • Multiple Myeloma
  • Plasmacytoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Initial Treatment With Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in Multiple Myeloma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IRB16-1138
  • NCT ID: NCT02969837

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
ElotuzumabEmplicitiE-KRd regimen
CarfilzomibKryprolisE-KRd regimen
LenalidomideRevlimidE-KRd regimen
DexamethasoneE-KRd regimen

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
E-KRd regimenExperimentalParticipants will receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone.
  • Elotuzumab
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
E-Rd RegimenExperimentalParticipants will receive elotuzumab, lenalidomide, and dexamethasone.
  • Elotuzumab
  • Lenalidomide
  • Dexamethasone

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of sCR
Time Frame:At the end of eight months
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Adverse events will be monitored in real time and discussed at a weekly data and safety monitoring conference.
Measure:Rate of MRD
Time Frame:At the end of four, eight, and twelve months for certain subjects.
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Through study completion an average of one year
Safety Issue:
Description:These events will be analyzed at differing points of time based on the individual subjects disease progression.
Measure:Progression free survival
Time Frame:Through study completion an average of one year
Safety Issue:
Description:These events will be analyzed at differing points of time based on the individual subjects disease progression.
Measure:Time to progression
Time Frame:Through study completion an average of one year
Safety Issue:
Description:These events will be analyzed at differing points of time based on the individual subjects disease progression.
Measure:Overall survival
Time Frame:Through study completion an average of one year
Safety Issue:
Description:These events will be analyzed at differing points of time based on the individual subjects disease progression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

Trial Keywords

  • Multiple Myeloma
  • Elotuzumab
  • Carfilzomib (Kyprolis)
  • Lenalidomide (Revlimid)
  • Dexamethasone (E-KRd)

Last Updated

October 7, 2019