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

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03361306
Collaborator
Bristol-Myers Squibb (Industry)
15
1
1
85.6
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This single arm, open-label phase II study is designed with the primary objective of evaluating the efficacy of induction therapy comprised of 4 cycles of carfilzomib, lenalidomide, dexamethasone and elotuzumab (KRd+elotuzumab) in terms of very good partial response or better (VGPR+) in subjects with relapsed and/or refractory MM, and comparing to relevant historical controls. Post induction, all subjects will undergo disease evaluation for assessment of the primary endpoint. Maintenance therapy comprised of elotuzumab and lenalidomide (R+elotuzumab) will start directly after induction and continue until relapse or progression.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
LCI-HEM-MYE-CRD-002: A Phase II Study of Carfilzomib- Revlimid-Dexamethasone-Elotuzumab in Relapsed/Refractory Multiple Myeloma
Actual Study Start Date :
Dec 15, 2017
Actual Primary Completion Date :
Jun 4, 2021
Anticipated Study Completion Date :
Feb 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: KRd-Elotuzumab

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
Experimental
Other Names:
  • Empliciti
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With VGPR or Better Response to Induction [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.]

      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.

    Secondary Outcome Measures

    1. 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.]

      Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by IMWG 2016 response criteria.

    2. Overall Survival (OS) [From date of treatment start to date of death, or censored as described; assessed for approximately 5 years.]

      OS is defined as the duration from treatment start date to the date of death from any cause. Subjects who are alive or lost to follow up at the time of the analysis will be censored at the last known date they were alive.

    3. Progression Free Survival (PFS) [From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.]

      PFS is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

    4. Time to Disease Progression (TTP) [From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.]

      TTP is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death related to disease progression. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If a subject died for causes related to disease progression then progression date will be date of death. If a subject died for causes other than disease progression, TTP will be censored at the date of other cause mortality. For surviving subjects who do not have PD, TTP will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, TTP will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial TTP event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

    5. Duration of Response (DoR) [From time of first response to date of progression/death, or censored as described; assessed for approximately 3 years.]

      DoR will be calculated for each subject with response for the VGPR+ and overall response endpoints. The DoR intervals will be calculated from the time of the first assessment that identified response until disease progression or death. The censoring mechanism for DoR will be the same as described for PFS.

    6. Time to Next Treatment (TTNT) [From treatment start date to date of next treatment, or censored as described; assessed for approximately 3 years.]

      TTNT will be calculated from the time of treatment start until the start of the first subsequent anti-cancer therapy after all protocol directed therapy is completed. For surviving subjects who do not receiving subsequent therapy, TTNT will be censored at the last contact date. For subjects who die before beginning subsequent anti-cancer therapy, TTNT will be censored at the date of death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Subject must meet all of the following applicable inclusion criteria to participate in this study:

    1. Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative.

    2. Age >= 18 years at the time of consent.

    3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (see Appendix A, Section 18.1).

    4. Documented history of relapsed and/or refractory multiple myeloma per IMWG 2016 criteria [22] as defined below (biochemical and/or clinical relapse per IMWG criteria); (NOTE: subjects refractory to bortezomib and/or lenalidomide are eligible; subjects who previously received carfilzomib are eligible provided they experienced a minimal response or better and relapsed >60 days after completion of treatment [see exclusion criteria #2]):

    5. Relapse is defined as progression of disease after an initial response to previous treatment, more than 6 months after discontinuation of treatment.

    6. 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.

    7. 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.

    8. Subject must have recovered from any treatment-induced toxicities to ≤ grade 1 or baseline

    9. Adequate washout from previous therapy:

    10. Prior chemotherapy is completed >3 weeks prior to day 1 of treatment (6 weeks for melphalan, nitrosoureas or monoclonal antibodies).

    11. 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.

    12. Prior radiotherapy completed at least 2 weeks prior to day 1 of treatment.

    13. Corticosteroid therapy at a dose equivalent to dexamethasone >4mg/day has been completed at least 2 weeks prior to day 1 of treatment.

    14. Measurable disease defined as:

    15. Serum M-protein > 0.5 g/dL OR

    16. Urine M-protein ≥200 mg/24 h OR

    17. Involved free light chain (FLC) level ≥10 mg/dL provided serum FLC ratio is abnormal.

    18. 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)

    19. 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.

    20. Females of childbearing potential (FCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to day 1 of treatment, and be willing to undergo serial serum or urine pregnancy testing. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).

    21. FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) plus a second contraceptive method (considered acceptable [failure rate of >1% per year] or highly effective) from the time of informed consent until 6 months after the last protocol prescribed therapy has been discontinued. NOTE: estrogens may further increase the risk of thrombosis (beyond that associated with lenalidomide) and their use should be based on a benefit-risk decision. For the highly effective contraceptive method, a method with low user dependency is preferable but not required (see tables, adapted from:

    http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2 014_09_HMA_CTFG_Contraception.pdf).

    1. Male subjects (even those who have had a vasectomy) who are sexually active with a FCBP must be willing to use latex or synthetic condoms from the time of informed consent until 180 days after the last protocol prescribed therapy has been discontinued. The FCBP partner should also consider contraception recommendations (see inclusion #11).

    2. As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study.

    Exclusion Criteria

    Subjects meeting any of the criteria below may not participate in the study:
    1. Discontinuation of previous lenalidomide, carfilzomib or dexamethasone due to intolerance.

    2. If previously treated with carfilzomib, lack of response, progression during or relapsed within 60 days after completion of treatment.

    3. Any infection, at the time of screening, requiring systemic therapy (i.e. involving IV antibiotics) (NOTE: at discretion of investigator, subjects with uncomplicated urinary tract infections may be eligible).

    4. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study, and any female subject must agree not to donate eggs during the study and for 4 months after the last protocol prescribed therapy has been discontinued).

    5. Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, carcinoma of the prostate with a current PSA value of <0.5 ng/mL or other cancer for which the subject has completed treatment, been disease-free for at least five years, and is considered by Sponsor-Investigator to be at <30% risk of relapse, or on hormonal therapy for a history of either prostate cancer or breast cancer, provided that there has been no evidence of disease progression during the previous three years.

    6. Non-secretory MM.

    7. Active involvement of the central nervous system by MM.

    8. Prior cardiovascular cerebrovascular accident with persistent neurological deficit.

    9. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

    10. Had major surgery within 4 weeks prior to day 1 of treatment.

    11. Plasmapheresis within 4 weeks from day 1 of treatment.

    12. Treatment with any investigational drug within 4 weeks prior to day 1 of treatment.

    13. Uncontrolled clinically significant illness including, but not limited to, uncontrolled hypertension (as per the most updated Joint National Committee for the Management of Hypertension definitions), symptomatic congestive heart failure (as per New York Heart Association [NYHA] class III or IV [see Appendix C, Section 18.3], uncontrolled angina pectoris, myocardial infarction within the past 6 months, known or suspected amyloidosis, uncontrolled cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator, or any other condition (including laboratory abnormalities) that would, in the opinion of the Sponsor-Investigator, place the subject at unacceptable risk if he/she were to participate in the study.

    14. Known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, elotuzumab or its excipients or known sensitivity to mammalian-derived products, carfilzomib or its excipients, lenalidomide or its excipients, or dexamethasone or its excipients.

    15. Known human immunodeficiency virus (HIV) infection or active hepatitis A, B and/or C infection.

    16. Subjects with resolved HBV infection (i.e. subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Subjects who are PCR positive will be excluded. Exception: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Levine Cancer Institute Charlotte North Carolina United States 28204

    Sponsors and Collaborators

    • Wake Forest University Health Sciences
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Manisha Bhutani, MD, Wake Forest University Health Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT03361306
    Other Study ID Numbers:
    • LCI-HEM-MYE-CRD-002
    First Posted:
    Dec 4, 2017
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Wake Forest University Health Sciences
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title KRd-Elotuzumab
    Arm/Group Description 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)
    Period Title: Overall Study
    STARTED 15
    COMPLETED 0
    NOT COMPLETED 15

    Baseline Characteristics

    Arm/Group Title KRd-Elotuzumab
    Arm/Group Description 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)
    Overall Participants 15
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    9
    60%
    >=65 years
    6
    40%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    Sex: Female, Male (Count of Participants)
    Female
    6
    40%
    Male
    9
    60%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    15
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    26.7%
    White
    11
    73.3%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    15
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With VGPR or Better Response to Induction
    Description 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.
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    The response evaluable population is defined as all subjects who initiate treatment with elotuzumab and who have measurable disease at baseline.
    Arm/Group Title KRd-Elotuzumab
    Arm/Group Description 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)
    Measure Participants 15
    Count of Participants [Participants]
    7
    46.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection KRd-Elotuzumab
    Comments
    Type of Statistical Test Superiority
    Comments Assuming the true VGPR+ rate is 40% under the null hypothesis, then this design will provide 90% power to detect a difference of 20% under the alternative hypothesis, assuming a one-sided alpha=0.10 significance level. For the originally planned enrollment of 40 subjects, if at least 21 subjects achieved VGPR or better to induction, the null hypothesis would be rejected.
    Statistical Test of Hypothesis p-Value 0.390
    Comments This p-value is only based on partial enrollment on the study. As enrollment was halted early, this p-value is descriptive in nature and cannot determine the success/failure of the trial.
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Response Rate
    Estimated Value 0.467
    Confidence Interval (2-Sided) 95%
    0.213 to 0.734
    Parameter Dispersion Type:
    Value:
    Estimation Comments Confidence interval estimated using the Clopper Pearson method.
    2. Secondary Outcome
    Title Number of Subjects With an Objective Response
    Description Objective response was determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of complete response (CR) or partial response (PR) as determined by IMWG 2016 response criteria.
    Time Frame From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    Title Overall Survival (OS)
    Description OS is defined as the duration from treatment start date to the date of death from any cause. Subjects who are alive or lost to follow up at the time of the analysis will be censored at the last known date they were alive.
    Time Frame From date of treatment start to date of death, or censored as described; assessed for approximately 5 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description PFS is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.
    Time Frame From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    Title Time to Disease Progression (TTP)
    Description TTP is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death related to disease progression. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If a subject died for causes related to disease progression then progression date will be date of death. If a subject died for causes other than disease progression, TTP will be censored at the date of other cause mortality. For surviving subjects who do not have PD, TTP will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, TTP will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial TTP event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.
    Time Frame From treatment start date to date of progression/death, or censored as described; assessed for approximately 3 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Secondary Outcome
    Title Duration of Response (DoR)
    Description DoR will be calculated for each subject with response for the VGPR+ and overall response endpoints. The DoR intervals will be calculated from the time of the first assessment that identified response until disease progression or death. The censoring mechanism for DoR will be the same as described for PFS.
    Time Frame From time of first response to date of progression/death, or censored as described; assessed for approximately 3 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Secondary Outcome
    Title Time to Next Treatment (TTNT)
    Description TTNT will be calculated from the time of treatment start until the start of the first subsequent anti-cancer therapy after all protocol directed therapy is completed. For surviving subjects who do not receiving subsequent therapy, TTNT will be censored at the last contact date. For subjects who die before beginning subsequent anti-cancer therapy, TTNT will be censored at the date of death
    Time Frame From treatment start date to date of next treatment, or censored as described; assessed for approximately 3 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Baseline, during treatment, and through 30 days after study treatment is discontinued, an average of 14 months.
    Adverse Event Reporting Description
    Arm/Group Title KRd-Elotuzumab
    Arm/Group Description Carfilzomib, Revlimid, Dexamethasone, Elotuzumab Elotuzumab: Experimental
    All Cause Mortality
    KRd-Elotuzumab
    Affected / at Risk (%) # Events
    Total 5/15 (33.3%)
    Serious Adverse Events
    KRd-Elotuzumab
    Affected / at Risk (%) # Events
    Total 8/15 (53.3%)
    Blood and lymphatic system disorders
    Anemia 2/15 (13.3%)
    Febrile neutropenia 1/15 (6.7%)
    Cardiac disorders
    Aortic valve disease 1/15 (6.7%)
    Gastrointestinal disorders
    Diarrhea 1/15 (6.7%)
    General disorders
    Death NOS 1/15 (6.7%)
    Fever 6/15 (40%)
    Infections and infestations
    Lung infection 1/15 (6.7%)
    Upper respiratory infection 1/15 (6.7%)
    Musculoskeletal and connective tissue disorders
    Bone pain 1/15 (6.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 1/15 (6.7%)
    Nervous system disorders
    Syncope 1/15 (6.7%)
    Psychiatric disorders
    Confusion 1/15 (6.7%)
    Renal and urinary disorders
    Acute kidney injury 1/15 (6.7%)
    Vascular disorders
    Hematoma 1/15 (6.7%)
    Thromboembolic event 2/15 (13.3%)
    Other (Not Including Serious) Adverse Events
    KRd-Elotuzumab
    Affected / at Risk (%) # Events
    Total 15/15 (100%)
    Blood and lymphatic system disorders
    Anemia 3/15 (20%)
    Cardiac disorders
    Cardiac disorders - Other 1/15 (6.7%)
    Cardiac disorders - Other 1/15 (6.7%)
    Aortic valve disease 1/15 (6.7%)
    Chest pain - cardiac 1/15 (6.7%)
    Palpitations 1/15 (6.7%)
    Sinus tachycardia 1/15 (6.7%)
    Ear and labyrinth disorders
    Vertigo 1/15 (6.7%)
    Eye disorders
    Blurred vision 2/15 (13.3%)
    Floaters 1/15 (6.7%)
    Gastrointestinal disorders
    Diarrhea 9/15 (60%)
    Constipation 6/15 (40%)
    Nausea 4/15 (26.7%)
    Mucositis oral 2/15 (13.3%)
    Vomiting 2/15 (13.3%)
    Abdominal pain 1/15 (6.7%)
    Dry mouth 1/15 (6.7%)
    Dyspepsia 1/15 (6.7%)
    Fecal incontinence 1/15 (6.7%)
    Flatulence 1/15 (6.7%)
    Gastroesophageal reflux disease 1/15 (6.7%)
    Toothache 1/15 (6.7%)
    General disorders
    Fatigue 9/15 (60%)
    Edema limbs 7/15 (46.7%)
    Pain 5/15 (33.3%)
    Fever 3/15 (20%)
    Injection site reaction 1/15 (6.7%)
    Chills 1/15 (6.7%)
    Infusion related reaction 1/15 (6.7%)
    Non-cardiac chest pain 1/15 (6.7%)
    Infections and infestations
    Upper respiratory infection 6/15 (40%)
    Sinusitis 2/15 (13.3%)
    Bronchial infection 1/15 (6.7%)
    Infections and infestations - Other 1/15 (6.7%)
    Lung infection 1/15 (6.7%)
    Rash pustular 1/15 (6.7%)
    Injury, poisoning and procedural complications
    Aortic Injury 1/15 (6.7%)
    Bruising 3/15 (20%)
    Fall 1/15 (6.7%)
    Fracture 1/15 (6.7%)
    Investigations
    Neutrophil count decreased 6/15 (40%)
    Platelet count decreased 4/15 (26.7%)
    Lymphocyte count decreased 3/15 (20%)
    Alanine aminotransferase increased 2/15 (13.3%)
    Aspartate aminotransferase increased 2/15 (13.3%)
    Blood bilirubin increased 2/15 (13.3%)
    Creatinine increased 2/15 (13.3%)
    Cholesterol high 1/15 (6.7%)
    Metabolism and nutrition disorders
    Hypophosphatemia 9/15 (60%)
    Hypokalemia 8/15 (53.3%)
    Hypocalcemia 5/15 (33.3%)
    Hypomagnesemia 5/15 (33.3%)
    Anorexia 4/15 (26.7%)
    Dehydration 3/15 (20%)
    Hyperglycemia 2/15 (13.3%)
    Hypertriglyceridemia 1/15 (6.7%)
    Hypoglycemia 1/15 (6.7%)
    Metabolism and nutrition disorders - Other 1/15 (6.7%)
    Musculoskeletal and connective tissue disorders
    Myalgia 6/15 (40%)
    Back pain 5/15 (33.3%)
    Pain in extremity 5/15 (33.3%)
    Muscle weakness lower limb 2/15 (13.3%)
    Neck pain 2/15 (13.3%)
    Arthralgia 1/15 (6.7%)
    Bone pain 1/15 (6.7%)
    Buttock pain 1/15 (6.7%)
    Flank pain 1/15 (6.7%)
    Generalized muscle weakness 1/15 (6.7%)
    Musculoskeletal and connective tissue disorder - Other 1/15 (6.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 1/15 (6.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other 1/15 (6.7%)
    Nervous system disorders
    Headache 7/15 (46.7%)
    Paresthesia 7/15 (46.7%)
    Dizziness 2/15 (13.3%)
    Dysesthesia 1/15 (6.7%)
    Dysgeusia 1/15 (6.7%)
    Neuralgia 1/15 (6.7%)
    Sinus pain 1/15 (6.7%)
    Psychiatric disorders
    Insomnia 5/15 (33.3%)
    Agitation 1/15 (6.7%)
    Depression 1/15 (6.7%)
    Libido decreased 1/15 (6.7%)
    Restlessness 1/15 (6.7%)
    Renal and urinary disorders
    Urinary incontinence 2/15 (13.3%)
    Acute kidney injury 1/15 (6.7%)
    Renal and urinary disorders - Other 1/15 (6.7%)
    Urinary retention 1/15 (6.7%)
    Urine discoloration 1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 9/15 (60%)
    Nasal congestion 7/15 (46.7%)
    Dyspnea 6/15 (40%)
    Postnasal drip 4/15 (26.7%)
    Sore throat 4/15 (26.7%)
    Productive cough 2/15 (13.3%)
    Epistaxis 1/15 (6.7%)
    Hoarseness 1/15 (6.7%)
    Laryngeal inflammation 1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders - Other 1/15 (6.7%)
    Skin and subcutaneous tissue disorders - Other 1/15 (6.7%)
    Skin and subcutaneous tissue disorders - Other 1/15 (6.7%)
    Skin and subcutaneous tissue disorders - Other 1/15 (6.7%)
    Hyperhidrosis 1/15 (6.7%)
    Vascular disorders
    Phlebitis 1/15 (6.7%)
    Flushing 5/15 (33.3%)
    Hypotension 2/15 (13.3%)
    Thromboembolic event 2/15 (13.3%)
    Hematoma 1/15 (6.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chair of Biostatistics Department
    Organization Levine Cancer Institute
    Phone 9804422371
    Email james.symanowski@atriumhealth.org
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT03361306
    Other Study ID Numbers:
    • LCI-HEM-MYE-CRD-002
    First Posted:
    Dec 4, 2017
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jan 1, 2022