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

NCT02969837 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB16-1138
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

This study was a multi-center, open-label, single-arm, Phase 2 study where newly diagnosed Multiple Myeloma requiring systemic chemotherapy will be eligible for enrollment. A total of 46 subjects were enrolled. The primary end point was the rate of stringent complete response (sCR) and/or MRD-negativity (10-5) after C8 Elo-KRd. Secondary end points included safety, rate of response, MRD status, PFS, and overall survival (OS).

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Stringent Complete Response (sCR)

  Response will be determined according to the International Myeloma Working Group (IMWG) response criteria for multiple myeloma. sCR is defined as CR plus : * normal FLC ratio and * absence of clonal cells in bone marrow by immunohistochemistry or 2 - 4 color flow cytometry CR is defined as below : * Negative immunofixation on the serum and urine and * disappearance of any soft tissue plasmacytomas and * \< 5% plasma cells in bone marrow. * In subjects with only FLC disease, a normal FLC ratio of 0.26-1.65 is required.

  Landmark evaluations were performed after cycles 4, 8, 12, 18 and 24 (that is, 4, 8, 12, 18 and 24 months)

• Number of Participants With MRD-negativity (10^-5) After C8 Elo-KRd

  Subjects will be tested for Minimal Residual Disease (MRD) by Next Generation Sequencing (NGS) and flow cytometry after cycle 8. The flow cytometry analysis procedure used to determine MRD is performed on a NAVIOS FLOW CYTOMETER SYSTEM manufactured by BECKMAN COULTER, INC., using a laboratory developed assay. The Premarket Notification 510(k) (Number K130373) for the device can be found using the following link. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K130373.

  Landmark evaluations were performed after cycle 8

• The Number of Participants With Stringent Complete Response (sCR) and/or MRD Negative (10^-5) by NGS

  Response will be determined according to the International Myeloma Working Group (IMWG) response criteria for multiple myeloma. sCR is defined as CR plus : * normal FLC ratio and * absence of clonal cells in bone marrow by immunohistochemistry or 2 - 4 color flow cytometry CR is defined as below : * Negative immunofixation on the serum and urine and * disappearance of any soft tissue plasmacytomas and * \< 5% plasma cells in bone marrow. * In subjects with only FLC disease, a normal FLC ratio of 0.26-1.65 is required. Subjects will be tested for Minimal Residual Disease (MRD) by Next Generation Sequencing (NGS) and flow cytometry after cycles 4,8,12,18 and 24. The flow cytometry analysis procedure used to determine MRD is performed on a NAVIOS FLOW CYTOMETER SYSTEM manufactured by BECKMAN COULTER, INC., using a laboratory developed assay.

  Landmark evaluations were performed after cycles 4, 8, 12, 18 and 24 (that is, 4, 8, 12, 18 and 24 months)

Secondary Outcomes (4)

• Number of Participants With Adverse Events of Elotuzumab in Combination With KRd

  AEs were recorded from the day of signed consent through 30 days after the last does of Elo-KRd or initiation of new therapy, an average of 2 years.

• Duration of Response

  Up to two years

• Median Progression Free Survival

  up to two years

• Median Overall Survival

  up to two years

Study Arms (1)

Elo-KRd regimen

EXPERIMENTAL

Subjects will be tested for Minimal Residual Disease (MRD) by Next Generation Sequencing (NGS) and flow cytometry after cycles 8 and 12. A treatment decision was made after cycle 12 based on these results. There are three outcomes based on the IFM trial (Avet-Loiseau et al., 2015): 1) if the subject is MRD-negative by NGS after cycle 8 and 12, the subject went on E-Rd maintenance until disease progression. 2) If the subject is MRD-positive after cycle 8 but MRD-negative after cycle 12, 6 more cycles of E-KRd was given and at the end of 18 cycles, the subject went on E-Rd maintenance until disease progression. 3) Finally, if the subject is MRD-positive at both instances, 12 additional cycles of E-KRd was given and at the end of 24 cycles total, the subject went on E-Rd maintenance until disease progression.

Drug: Elotuzumab; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Elotuzumab DRUG

Elotuzumab will be given on Cycles 1-2 on days 1, 8, 15, 22, Cycles 3 and Beyond on days 1 and 15

Also known as: Empliciti

Elo-KRd regimen

Carfilzomib DRUG

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

Also known as: Kryprolis

Elo-KRd regimen

Lenalidomide DRUG

Lenalidomide will be given on days 1-21 for all cycles.

Also known as: Revlimid

Elo-KRd regimen

Dexamethasone DRUG

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

Elo-KRd regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• x serum creatinine in mg/dL
• o Male CrCl = (140 - age in years) x weight in kg x 1.00

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Chicago: lead
• Bristol-Myers Squibb: collaborator
• Amgen: collaborator
• Multiple Myeloma Research Foundation: collaborator

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Derman BA, Kansagra A, Zonder J, Stefka AT, Grinblatt DL, Anderson LD Jr, Gurbuxani S, Narula S, Rayani S, Major A, Kin A, Jiang K, Karrison T, Jasielec J, Jakubowiak AJ. Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. JAMA Oncol. 2022 Sep 1;8(9):1278-1286. doi: 10.1001/jamaoncol.2022.2424.

  PMID: 35862034 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; carfilzomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Member of the Biostatistics Lab
• Organization: University of Chicago

slee@health.bsd.uchicago.edu

773.702.2453

Study Officials

• Andrzej Jakubowiak, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 21, 2016
• Study Start: July 10, 2017
• Primary Completion: October 11, 2021
• Study Completion: December 1, 2025
• Last Updated: January 16, 2026
• Results First Posted: September 10, 2025

Record last verified: 2025-12

Locations

US (3)