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

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ClinicalTrials.gov Identifier: NCT03275285
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

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 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
Plasma Cell Myeloma Drug: isatuximab SAR650984 Drug: carfilzomib Drug: dexamethasone 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 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 : October 25, 2017
Estimated Primary Completion Date : August 24, 2023
Estimated Study Completion Date : August 24, 2023


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


Drug: carfilzomib

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: 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 Name: Kyprolis

Drug: dexamethasone

Pharmaceutical form: tablets or solution for infusion

Route of administration: oral or intravenous





Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to approximately 36 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) [ Time Frame: Up to approximately 36 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 [ Time Frame: Up to approximately 36 months ]
    The proportion of patients with sCR, CR and VGPR

  3. CR rate [ Time Frame: Up to approximately 36 months ]
    The proportion of patients with sCR and CR

  4. Rate of VGPR or better with MRD (Minimal Residual Disease) negativity [ Time Frame: Up to approximately 36 months ]
    The proportion of patients with VGPR, CR or sCR and for whom MRD assessed by sequencing is negative

  5. Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
    The length of time from the treatment allocation for a disease that patients are still alive

  6. Time to Progression (TTP) [ Time Frame: Up to approximately 36 months ]
    How long the study treatment last before disease progression occurs

  7. Second Progression Free Survival (PFS2) [ Time Frame: Up to approximately 36 months ]
    The length of time between treatment allocation and second progression disease

  8. Duration of response (DOR) [ Time Frame: Up to approximately 36 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 [ Time Frame: 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 [ Time Frame: Screening to 90 days after last study treatment administration ]
    To evaluate change in your daily activities from screening

  11. Pharmacokinetics of isatuximab [ Time Frame: Up to approximately 10 months ]
    To evaluate the plasma concentration of isatuximab

  12. Pharmacokinetics of carfilzomib [ Time Frame: Up to 1 month ]
    To evaluate the plasma concentration of carfilzomib in 12 patients

  13. Immunogenicity (ADA) [ Time Frame: Up to 13 months ]
    To evaluate presence of anti-drug antibodies against isatuximab



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275285


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

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Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03275285     History of Changes
Other Study ID Numbers: EFC15246
2017-001940-37 ( EudraCT Number )
U1111-1195-5957 ( Other Identifier: UTN )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors