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IKEMA: Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients

Sponsor
Sanofi (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03275285
Collaborator
(none)
302
Enrollment
70
Locations
2
Arms
63.4
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the benefit of isatuximab in combination with carfilzomib and dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to carfilzomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM) previously treated with 1 to 3 lines of therapy.

Secondary Objectives:

  • To evaluate the Overall Response Rate (ORR), rate of very good partial response (VGPR) or better and complete response (CR) rate in both arms using International Myeloma Working Group (IMWG) criteria.

  • To evaluate rate of VGPR or better with minimal residual disease (MRD) negativity in both arms using IMWG criteria.

  • To evaluate the Overall Survival (OS) in both arms.

  • To evaluate safety in both arms.

  • To evaluate duration of response (DOR) in both arms.

  • To evaluate the Time To Progression (TTP) in both arms.

  • To evaluate the Second Progression Free Survival (PFS2) in both arms.

  • To evaluate the Time to first response

  • To evaluate the Time to best response

  • To determine the Pharmacokinetic profile of isatuximab in combination with carfilzomib.

  • To evaluate the immunogenicity of isatuximab in isatuximab arm.

  • To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status in both arms.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The duration of the study for the patients will include a period for screening of up to 3 weeks. Patients will continue study treatment until disease progression, unacceptable adverse reaction, patients' wish or other reason of discontinuation. During follow-up, patients who discontinue the study treatment due to progression of the disease will be followed every 3 months (12 weeks) for further anti-myeloma therapies, progression free survival to the second progression and survival, until death or the cut-off date, whichever comes first. Patients who discontinue the study treatment prior to documentation of disease progression will be followed-up every 4 weeks until confirmation of disease progression, and then every 3 months (12 weeks) for further anti-myeloma therapies, progression free survival to the second progression and survival, until death or the cut-off date, whichever comes first. After progression free survival analysis, patients will be followed yearly for 3 years for survival.

Study Design

Study Type:
Interventional
Actual Enrollment :
302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized, Open Label, Multicenter Study Assessing The Clinical Benefit Of Isatuximab Combined With Carfilzomib (Kyprolis®) And Dexamethasone Versus Carfilzomib With Dexamethasone In Patients With Relapse And/Or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines
Actual Study Start Date :
Oct 25, 2017
Actual Primary Completion Date :
Jan 21, 2022
Anticipated Study Completion Date :
Feb 7, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Isatuximab + Carfilzomib + Dexamethasone (IKd)

Isatuximab (intravenous) on day 1, 8, 15 and 22 of 1st cycle, then on day 1 and 15 of subsequent cycles in combination with carfilzomib (intravenous) on day 1, 2, 8, 9, 15 and 16 + dexamethasone (intravenous or by mouth [po]) on day 1, 2, 8, 9, 15, 16, 22 and 23 of a 28 day cycle

Drug: isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous
Other Names:
  • Sarclisa

    • Drug: carfilzomib
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Kyprolis

    • Drug: dexamethasone
    Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous
    Active Comparator: Carfilzomib + Dexamethasone (Kd)

    Carfilzomib (intravenous) on day 1, 2, 8, 9, 15, 16 + dexamethasone (intravenous or po) on day 1, 2, 8, 9, 15, 16, 22 and 23 of a 28 day cycle

    Drug: carfilzomib
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Kyprolis

    • Drug: dexamethasone
    Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [Up to approximately 60 months]

      The length of time between treatment allocation and a patient lives with the disease but it does not get worse

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Up to approximately 60 months]

      The proportion of patients that have a response to their disease: stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR)

    2. Rate of VGPR or better [Up to approximately 60 months]

      The proportion of patients with sCR, CR and VGPR

    3. CR rate [Up to approximately 60 months]

      The proportion of patients with sCR and CR

    4. Rate of VGPR or better with MRD (Minimal Residual Disease) negativity [Up to approximately 60 months]

      The proportion of patients for whom MRD assessed by sequencing is negative at any time after first dose of study treatment

    5. Overall Survival (OS) [Up to approximately 60 months]

      The length of time from the treatment allocation for a disease that patients are still alive

    6. Time to Progression (TTP) [Up to approximately 60 months]

      How long the study treatment last before disease progression occurs

    7. Second Progression Free Survival (PFS2) [Up to approximately 60 months]

      The length of time between treatment allocation to the date of first documentation of PD after initiation of further anti-myeloma treatment or death from any cause, whichever happens first

    8. Duration of response (DOR) [Up to approximately 60 months]

      How long from the first response is observed until disease progression

    9. Number of patients with adverse events according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grading scaling [Up to 30 days after last study treatment administration]

      To evaluate how many adverse events occur while taking study treatment

    10. Patient-reported outcome measured with Quality of Life questionnaire [Screening to 90 days after last study treatment administration]

      To evaluate change in daily activities from screening

    11. Pharmacokinetics of isatuximab [Up to approximately 10 months]

      To evaluate the plasma concentration of isatuximab

    12. Pharmacokinetics of carfilzomib [Up to 1 month]

      To evaluate the plasma concentration of carfilzomib in 12 patients

    13. Immunogenicity (ADA) [Up to 13 months]

      To evaluate presence of anti-drug antibodies against isatuximab

    14. Time to first response [Up to approximately 60 months]

      Length of time from treatment allocation to the date of first response (PR or better)

    15. Time to best response [Up to approximately 60 months]

      Length of time from treatment allocation to the date of first best overall response (PR or better)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:
    • Patients with multiple myeloma previously treated with prior 1 to 3 lines and with measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours).
    Exclusion criteria:

    • Patients previously pretreated with carfilzomib, who never achieved at least one minor response during previous therapies and/or last previous therapy completed within 14 last days.

    • Patients with serum free light chain (FLC) measurable disease only.

    • Patients less than 18 years old, patients with Eastern Cooperative Oncology Group performance status more than 2.

    • Patients with inadequate biological tests.

    • Patients with myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, superior or equal to grade 3 arrhythmias, stroke or transient ischemic attack within last 6 months, and/or left ventricular ejection fraction lower than 40%.

    • Patients with previous cancer unless disease free for more than 5 years or in situ cancer curatively treated.

    • Patients with known acquired immunodeficiency syndrome related illness (AIDS) or human immunodeficiency virus (HIV) requiring antiretroviral treatment, or hepatitis A, B, or C active infection.

    • Women of childbearing potential or male patient with women of childbearing potential who do not agree to use highly effective method of birth control.

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Number 8400002 San Francisco California United States 94117
    2 Investigational Site Number 8400003 Spartanburg South Carolina United States 29303-3040
    3 Investigational Site Number 0360005 Blacktown Australia 2148
    4 Investigational Site Number 0360001 Fitzroy Australia 3065
    5 Investigational Site Number 0360004 Heidelberg West Australia 3081
    6 Investigational Site Number 0360007 Nedlands Australia 6009
    7 Investigational Site Number 0360006 Tweed Heads Australia 2485
    8 Investigational Site Number 0360008 West Perth Australia 6005
    9 Investigational Site Number 0360002 Wollongong Australia 2500
    10 Investigational Site Number 0760001 Barretos Brazil 14784-400
    11 Investigational Site Number 0760003 Porto Alegre Brazil 90110-270
    12 Investigational Site Number 0760004 Rio De Janeiro Brazil 22793-080
    13 Investigational Site Number 0760005 Salvador Brazil 40110-090
    14 Investigational Site Number 0760002 Sao Paulo Brazil 05403-000
    15 Investigational Site Number 1240002 Montreal Canada H1T 2M4
    16 Investigational Site Number 1240001 Saint John Canada E2L 4L2
    17 Investigational Site Number 1240003 Surrey Canada V3V 1Z2
    18 Investigational Site Number 2030002 Brno Czechia 62500
    19 Investigational Site Number 2030004 Olomouc Czechia 77900
    20 Investigational Site Number 2030003 Ostrava - Poruba Czechia 70852
    21 Investigational Site Number 2030001 Praha 2 Czechia 12808
    22 Investigational Site Number 2500003 Lille France 59037
    23 Investigational Site Number 2500001 Nantes France 44093
    24 Investigational Site Number 2500006 Paris France 75012
    25 Investigational Site Number 2500002 Pessac France 33600
    26 Investigational Site Number 2500005 Pierre Benite Cedex France 69495
    27 Investigational Site Number 2500004 Poitiers Cedex France 86021
    28 Investigational Site Number 3000002 Athens Greece 10676
    29 Investigational Site Number 3000005 Athens Greece 11527
    30 Investigational Site Number 3000001 Athens Greece 11528
    31 Investigational Site Number 3000004 Patra Greece 26504
    32 Investigational Site Number 3000003 Thessaloniki Greece 57010
    33 Investigational Site Number 3480003 Budapest Hungary 1083
    34 Investigational Site Number 3480001 Budapest Hungary 1097
    35 Investigational Site Number 3480004 Budapest Hungary 1125
    36 Investigational Site Number 3480005 Kaposvár Hungary 7400
    37 Investigational Site Number 3800003 Bologna Italy 40138
    38 Investigational Site Number 3800001 Pisa Italy 56126
    39 Investigational Site Number 3800004 Reggio Emilia Italy 42123
    40 Investigational Site Number 3800002 Torino Italy 10126
    41 Investigational Site Number 3920007 Kumamoto-Shi Japan
    42 Investigational Site Number 3920004 Shibuya-Ku Japan
    43 Investigational Site Number 3920006 Shinjuku-Ku Japan
    44 Investigational Site Number 3920005 Shiwa-Gun Japan
    45 Investigational Site Number 3920003 Sunto-Gun Japan
    46 Investigational Site Number 3920001 Suwa-Shi Japan
    47 Investigational Site Number 3920002 Yamagata-Shi Japan
    48 Investigational Site Number 4100006 Busan Korea, Republic of 49201
    49 Investigational Site Number 4100002 Gangnam-Gu Korea, Republic of 06351
    50 Investigational Site Number 4100001 Seoul Korea, Republic of 03080
    51 Investigational Site Number 4100004 Seoul Korea, Republic of 03722
    52 Investigational Site Number 4100005 Seoul Korea, Republic of 06591
    53 Investigational Site Number 5540001 Auckland New Zealand 2025
    54 Investigational Site Number 5540002 Wellington New Zealand
    55 Investigational Site Number 6430002 Ekaterinburg Russian Federation 620102
    56 Investigational Site Number 6430003 Kirov Russian Federation 610027
    57 Investigational Site Number 6430004 Novosibirsk Russian Federation 630047
    58 Investigational Site Number 7240001 Badalona Spain 08916
    59 Investigational Site Number 7240005 Barcelona Spain 08036
    60 Investigational Site Number 7240003 Madrid Spain 28041
    61 Investigational Site Number 7240004 Sevilla Spain 41013
    62 Investigational Site Number 7240002 Valencia Spain 46017
    63 Investigational Site Number 7920003 Adana Turkey 01250
    64 Investigational Site Number 7920001 Ankara Turkey 06500
    65 Investigational Site Number 7920005 Bursa Turkey 16059
    66 Investigational Site Number 7920002 İstanbul Turkey
    67 Investigational Site Number 7920004 Samsun Turkey 55139
    68 Investigational Site Number 8260001 Bristol United Kingdom BS2 8ED
    69 Investigational Site Number 8260005 Leicester United Kingdom LE1 5WW
    70 Investigational Site Number 8260004 Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • Sanofi

    Investigators

    • Study Director: Clinical Sciences & Operations, Sanofi

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT03275285
    Other Study ID Numbers:
    • EFC15246
    • 2017-001940-37
    • U1111-1195-5957
    First Posted:
    Sep 7, 2017
    Last Update Posted:
    May 12, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sanofi
    Anti-CD38 monoclonal antibody
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone

    Study Results

    No Results Posted as of May 12, 2022