Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03194867
Recruitment Status : Active, not recruiting
First Posted : June 21, 2017
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE June 19, 2017
First Posted Date  ICMJE June 21, 2017
Last Update Posted Date July 15, 2019
Actual Study Start Date  ICMJE February 21, 2018
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
  • Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 4 weeks ]
    DLTs are following AEs in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AE
  • Adverse events (AEs) and changes in laboratory tests and vital signs [ Time Frame: Up to 90 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization ]
    Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
  • Overall Response Rate (ORR) [ Time Frame: Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 4 weeks ]
    DLTs are following AEs in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AE
  • Adverse events (AEs) and changes in laboratory tests and vital signs [ Time Frame: Up to 30 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization ]
    Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
  • Overall Response Rate (ORR) [ Time Frame: Up to 6 months from last patient in (LPI) for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR)
Change History Complete list of historical versions of study NCT03194867 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
  • Duration of Response (DOR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
  • Time to Response (TTR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
  • Progression Free Survival (PFS) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    PFS is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause
  • Overall Survival (OS) [ Time Frame: Up to 12 months from LPI for the final analysis ]
    OS defined as the time from the first study treatment administration to death from any cause
  • Assessment of PK parameter: partial AUC [ Time Frame: Up to 4 weeks ]
    AUC is area under the drug concentration versus time curve
  • Assessment of PK parameter: Cmax [ Time Frame: Up to 4 weeks ]
    Cmax is maximum drug concentration observed
  • Antibodies to isatuximab [ Time Frame: Up to 12 months from LPI for the final analysis ]
    Levels of anti isatuximab antibodies in plasma samples will be determined
  • Antibodies to cemiplimab [ Time Frame: Up to 12 months from LPI for the final analysis ]
    Levels of anti cemiplimab antibodies in serum samples will be determined
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimal response (MR)
  • Duration of Response (DOR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first
  • Time to Response (TTR) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    TTR is defined as time from first study treatment administration to first response (≥PR) that is subsequently confirmed
  • Progression Free Survival (PFS) [ Time Frame: Up to 6 months from LPI for primary efficacy analysis, and up to 12 months from LPI for the final analysis ]
    PFS is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause
  • Overall Survival (OS) [ Time Frame: Up to 12 months from LPI for the final analysis ]
    OS defined as the time from the first study treatment administration to death from any cause
  • Assessment of PK parameter: partial AUC [ Time Frame: Up to 4 weeks ]
    AUC is area under the drug concentration versus time curve
  • Assessment of PK parameter: Cmax [ Time Frame: Up to 4 weeks ]
    Cmax is maximum drug concentration observed
  • Antibodies to isatuximab [ Time Frame: Up to 12 months from LPI for the final analysis ]
    Levels of anti isatuximab antibodies in plasma samples will be determined
  • Antibodies to REGN2810 [ Time Frame: Up to 12 months from LPI for the final analysis ]
    Levels of anti REGN2810 antibodies in serum samples will be determined
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
Official Title  ICMJE A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma
Brief Summary

Primary Objectives:

  • To evaluate the safety and tolerability of the combination of isatuximab (also known as SAR650984) and cemiplimab (also known as REGN2810) in patients with relapse/refractory multiple myeloma.
  • To compare the overall response of the combination of isatuximab and cemiplimab versus isatuximab alone in patients with RRMM based on International Myeloma Working Group (IMWG) criteria.

Secondary Objectives:

  • To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS).
  • To assess the pharmacokinetics (PK) of isatuximab and cemiplimab when given in combination.
  • To assess the immunogenicity of isatuximab and cemiplimab when given in combination.
Detailed Description The duration of the study for a patient will include a period for screening of up to 21 days and 3-month post treatment follow up. The cycle duration is 28 days. Patients will continue treatment until disease progression, unacceptable adverse events, consent withdrawal, or any other reason.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Plasma Cell Myeloma
Intervention  ICMJE
  • Drug: Isatuximab SAR650984

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

  • Drug: Cemiplimab REGN2810

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

Study Arms  ICMJE
  • Experimental: Isatuximab/cemiplimab (Regimen 1)

    Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression.

    Cemiplimab on Days 1 and 15 in 28-day cycle up to disease progression.

    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Cemiplimab REGN2810
  • Experimental: Isatuximab/cemiplimab (Regimen 2)

    Isatuximab on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression.

    Cemiplimab on Day 1 in 28-day cycle up to disease progression.

    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Cemiplimab REGN2810
  • Active Comparator: Isatuximab
    Isatuximab on Days 1, 8, 15 and 22, then Day 1 and 15 in 28-day cycles up to disease progression.
    Intervention: Drug: Isatuximab SAR650984
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 12, 2019)
109
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2017)
54
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:

    • Serum M-protein ≥1 g/dL (≥0.5 g/dL in case of immunoglobulin A [IgA] disease), AND/OR
    • Urine M-protein ≥200 mg/24 hours, OR
    • In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (<0.26 or >1.65).
  • Patients must have received prior treatment with an immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment).
  • Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line).
  • Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible).

Exclusion criteria:

  • Prior exposure to isatuximab or participated clinical studies with isatuximab.
  • Prior exposure to any agent (approved or investigational) that blocks the programmed cell death-1 (PD-1)/PD-L1 pathway.
  • Evidence of other immune related disease/conditions.
  • History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation.
  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
  • Has allogenic haemopoietic stem cell (HSC) transplant.
  • Prior treatment with idelalisib (a PI3K inhibitor).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2.
  • Poor bone marrow reserve.
  • Poor organ function.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   Czechia,   France,   Greece,   Hungary,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03194867
Other Study ID Numbers  ICMJE TCD14906
2017-001431-39 ( EudraCT Number )
U1111-1189-4706 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP