LCI-HEM-MYE-CRD-002: Carfilzomib-Revlimid-Dexamethasone-Elotuzumab in Relapsed/Refractory Multiple Myeloma

NCT03361306 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LCI-HEM-MYE-CRD-00200023493
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study drug elotuzumab, has been clinically shown to be effective in treating relapsed/refractory MM in combination with either bortezomib, or lenalidomide and dexamethasone. Elotuzumab in combination with lenalidomide and dexamethasone is currently approved by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma. Carfilzomib is also FDA approved for treating multiple myeloma and frequently given in combination with lenalidomide and dexamethasone for treatment of relapsed/refractory MM. Based on these findings, this study will look at how subjects with relapsed/refractory MM respond to a combination treatment with the following drugs: elotuzumab, carfilzomib, lenalidomide and dexamethasone. The combination of these four drugs is not FDA approved and is experimental.

Conditions

Multiple Myeloma

Keywords

Relapsed

Outcome Measures

Primary Outcomes (1)

• Number of Participants With VGPR or Better Response to Induction

  The primary endpoint is a binary variable determined for each subject indicating whether the subject achieved a very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) to induction treatment with KRd-Elo, as defined by the IMWG 2016 response criteria. Per IMWG 2016 criteria, VGPR is defined as serum/urine M-protein detectable by immunofixation but not electrophoresis OR \>= 90% reduction in serum M protein plus urine M-protein \<100 mg/24 h. CR is defined as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow aspirates. sCR is defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry.

  From enrollment to the disease response determined at the end of the induction part of regimen (4 cycles of KRd-Elo was planned, but some subjects progressed before the end of induction). The median length of induction was 16 weeks.

Secondary Outcomes (6)

• Number of Subjects With an Objective Response

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity. Subjects were on treatment for a median of 12 months.

• Overall Survival (OS)

  From date of treatment start to date of death, or censored as described; assessed for approximately 5 years.

• Progression Free Survival (PFS)

  From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.

• Time to Disease Progression (TTP)

  From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.

• Duration of Response (DoR)

  From time of first response to date of progression/death, or censored as described; assessed for approximately 3 years.

Study Arms (1)

KRd-Elotuzumab

EXPERIMENTAL

Induction (4 28-day cycles): Carfilzomib (IV) @ 20 mg/m\^2, Day 1 of Cycle 1; @ 56 mg/m\^2, Day 8,15 of Cycle 1; @ 56 mg/m\^2, Day 1,8,15 of Cycles 2-4 Lenalidomide (Oral) @ 25 mg, once daily at bedtime on Days 1-21 of each cycle (Cycles 1-4) Dexamethasone @ 28 mg orally OR 8 mg IV, once weekly on Day 1,8,15,22 of Cycles 1-2; @28 mg orally OR 8 mg IV on Day 1 of Cycles 3-4 Elotuzumab (IV) @ 10 mg/kg, once weekly on Day 1,8,15,22 of Cycles 1-2; @ 20 mg/kg on Day 1 of Cycles 3-4 Maintenance (28-day cycles): Elotuzumab (IV) @ 20 mg/kg, Day 1 of each cycle (Cycles 1-n) Lenalidomide (Oral) @ 15 mg (or last tolerated dose if \<15 mg), once daily at bedtime on Days 1-21 of each cycle (Cycles 1-n)

Drug: Elotuzumab

Interventions

Elotuzumab DRUG

Experimental

Also known as: Empliciti

KRd-Elotuzumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative.
• Age \>= 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (see Appendix A, Section 18.1).

You may not qualify if:

• Relapse is defined as progression of disease after an initial response to previous treatment, more than 6 months after discontinuation of treatment.
• Refractory is defined as lack of response to previous treatment, progression of disease during treatment, or progression of disease within 6 months of discontinuation of treatment.
• Prior treatment with one line (and no more than one line) of systemic therapy for MM; NOTE: A new line of therapy is considered to start when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a result of progressive disease (PD), relapse, or toxicity or when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease. Induction therapy and stem cell transplant followed by planned maintenance therapy (provided there is no intervening PD) are considered to be a single line.
• Subject must have recovered from any treatment-induced toxicities to ≤ grade 1 or baseline
• Adequate washout from previous therapy:
• Prior chemotherapy is completed \>3 weeks prior to day 1 of treatment (6 weeks for melphalan, nitrosoureas or monoclonal antibodies).
• Autologous transplant completed (referring to day of stem cell infusion) \>12 weeks prior to day 1 of treatment; allogeneic transplant \>16 weeks prior to day 1 of treatment.
• Prior radiotherapy completed at least 2 weeks prior to day 1 of treatment.
• Corticosteroid therapy at a dose equivalent to dexamethasone \>4mg/day has been completed at least 2 weeks prior to day 1 of treatment.
• Measurable disease defined as:
• Serum M-protein \> 0.5 g/dL OR
• Urine M-protein ≥200 mg/24 h OR
• Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratio is abnormal.
• Demonstrate adequate organ function within 1 week of day 1 of treatment as defined in the table in Sec.tion 3.2 of protocol (#8)
• Adequate cardiac function as defined by ≥45% Left Ventricular Ejection Fraction (LVEF) by ECHO or MUGA within 28 days prior to day 1 of treatment.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Bristol-Myers Squibb: collaborator
• Atrium Health Levine Cancer Institute: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (1)

• Bhutani M, Foureau DM, Robinson M, Guo F, Fesenkova K, Atrash S, Paul B, Varga C, Friend R, Pineda-Roman M, Rigby K, Symanowski JT, Norek S, Tucker MR, Druhan LJ, Voorhees PM, Usmani SZ. A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse. Clin Lymphoma Myeloma Leuk. 2023 Jul;23(7):535-544.e1. doi: 10.1016/j.clml.2023.03.016. Epub 2023 Apr 7.

  PMID: 37127471 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

elotuzumab

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Manisha Bhutani, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 4, 2017
• Study Start: January 9, 2018
• Primary Completion: June 4, 2021
• Study Completion: February 14, 2025
• Last Updated: March 6, 2026
• Results First Posted: July 26, 2022

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)