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SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05405166
Recruitment Status : Recruiting
First Posted : June 6, 2022
Last Update Posted : September 2, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

This is a randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants will be randomized 1:1 into 1 of 2 study arms:

Arm SC: Isatuximab SC + Pd

Arm IV: Isatuximab IV + Pd

Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.


Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Recurrent Drug: Isatuximab IV Drug: Isatuximab SC Drug: Dexamethasone Drug: Pomalidomide Phase 3

Detailed Description:
Two study arms will be treated in 4-week cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 534 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 3, Open Label Study Evaluating Subcutaneous Versus Intravenous Administration of Isatuximab in Combination With Pomalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM)
Actual Study Start Date : June 23, 2022
Estimated Primary Completion Date : May 23, 2024
Estimated Study Completion Date : October 23, 2026


Arm Intervention/treatment
Experimental: Isatuximab Subcutaneous (SC)
Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days).
Drug: Isatuximab SC
Pharmaceutical form: Solution for subcutaneous administration; Route of administration: Subcutaneous (SC)
Other Name: SAR650984

Drug: Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral

Drug: Pomalidomide
Pharmaceutical form: hard capsules; Route of administration: Oral
Other Name: Pomalyst

Active Comparator: Isatuximab Intravenous (IV)
Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days).
Drug: Isatuximab IV
Pharmaceutical form: Concentrate solution for IV infusion; Route of administration: Intravenous
Other Names:
  • SAR650984
  • SARCLISA®

Drug: Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral

Drug: Pomalidomide
Pharmaceutical form: hard capsules; Route of administration: Oral
Other Name: Pomalyst




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to approximately 2 years ]
    ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC).

  2. Observed concentration before dosing (Cthrough) at steady state [ Time Frame: Predose at Cycle 6 Day 1 (duration of each cycle is 28 days) ]
    Observed Isatuximab plasma concentration


Secondary Outcome Measures :
  1. Very Good Partial Response or better rate (VGPR) [ Time Frame: Up to approximately 2 years ]
    Very Good Partial Response or better rate defined as the proportion of participants with stringent complete response (sCR), complete response (CR) and very good partial response (VGPR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).

  2. Observed concentration before dosing (Ctrough) [ Time Frame: At 4 weeks i.e., predose at Cycle 2 Day 1 (duration of each cycle is 28 days) ]
    Observed Isatuximab plasma concentration

  3. Incidence rate of infusion-reactions [ Time Frame: Up to approximately 4 years ]
    Proportion of participants with infusion-reactions related events

  4. Percentage of participants satisfied or very satisfied with the injection method used to administer study medication [ Time Frame: At Cycle 5 Day 15 ]
    Participant's satisfaction with isatuximab subcutaneous (SC) and intravenous (IV) will be assessed based on the Patient Experience and Satisfaction Questionnaires (PESQ) questionnaire.

  5. Duration of response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR, defined as the time from the date of the first confirmed response to the date of first occurrence of progressive disease (PD) as determined by IRC or death, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). In the absence of PD or death before the analysis cut-off date, the DOR will be censored at the date of the last valid disease assessment performed prior to initiation of a further anti-myeloma treatment or the analysis cut-off date, whichever is earlier. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.

  6. Time to first response (TT1R) [ Time Frame: Up to approximately 2 years ]
    TT1R, defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint.

  7. Time to best response (TTBR) [ Time Frame: Up to approximately 2 years ]
    TTBR, defined as the time from randomization to the date of first occurrence of IRC determined best overall response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint

  8. Progression free survival (PFS) [ Time Frame: Up to approximately 4 years ]
    PFS, defined as the time from the date of randomization to the date of first documentation of progressive disease as determined by IRC or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments. PFS will be censored at the date of the last valid disease assessment not showing disease progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.

  9. Overall survival (OS) [ Time Frame: Up to approximately 4 years ]
    OS, defined as the time from the date of randomization to death from any cause. Participants without death prior to the analysis cut-off date will be censored at the last date the participant was known to be alive or the cut-off date, whichever is first.

  10. Progression free survival 2 (PFS2) [ Time Frame: Up to approximately 4 years ]
    PFS2, defined as time from the date of randomization to the date of first documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment or death from any cause, whichever happens first. Same censoring rule applies as in the PFS endpoint.

  11. Number of participants with treatment-emergent adverse events (TEAEs)/serious adverse events (SAEs). [ Time Frame: Up to approximately 4 years ]
    Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.

  12. Pharmacokinetic (PK) parameter [ Time Frame: Up to approximately 4 years ]
    Maximum plasma concentration (Cmax)

  13. PK parameter [ Time Frame: Up to approximately 4 years ]
    Area under the plasma concentration time curve over the dosing period (AUC)

  14. Successful injection rate [ Time Frame: Up to approximately 4 years ]
    Number of successful injections with (investigational) isatuximab injector device divided by total number of actual injections

  15. Percentage of participants with anti-drug antibodies (ADA) against isatuximab [ Time Frame: Up to approximately 4 years ]
    An ADA positive patient was defined as a subject either having treatment-induced ADA response (no positive ADA response at baseline and any positive response in the post baseline period, including the follow-up visit) or a treatment-boosted ADA response (a positive ADA response at baseline and a ≥4-fold increase in titer in the post baseline period including the follow-up visit).

  16. Participant expectation questionnaire-baseline (PEQ-BL) score [ Time Frame: Cycle 1 Day 1 ((duration of each cycle is 28 days) ]
    PEQ-BL is designed to assess the expectations of the participants regarding both the treatment (side effects, worth taking) and the administration method (confidence, comfortability, pain, side effects, potential time-savings), as well as to understand previous treatment experience from the participant (experience with injection methods for oncology medication).

  17. Patient experience and satisfaction questionnaire- follow up (PESQ-FU) score [ Time Frame: Up to approximately 4 years ]
    PESQ-FU, a 9-item questionnaire is designed to follow up on participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction).

  18. Patient experience and satisfaction questionnaire-end of treatment (PESQ-EOT) score [ Time Frame: Up to approximately 4 years ]
    PESQ-EOT, a 17-item questionnaire is designed to assess participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction). This questionnaire includes also additional items to assess participant preference on injection method (subcutaneous or intravenous) and location of administration (at home or at clinic).

  19. Change from baseline in the Health Resource Utilization and Productivity Questionnaire (HRUPQ) scores [ Time Frame: Baseline; up to approximately 4 years ]
    Medical resource utilization and participant productivity will be collected from participants through the HRUPQ questionnaire. The questions include number, nature (emergency or routine) and duration of hospitalizations; emergency room visits and outpatient medical encounters; and employment history. The HRUPQ contains 46 items.

  20. Change from baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score [ Time Frame: Baseline; up to approximately 4 years ]
    EORTC QLQ-C30 is a cancer-specific questionnaire that contains 30 items and provides a multidimensional assessment of Health Related Quality of Life (HRQL).

  21. Change from baseline in European Organization for Research and Treatment of Cancer quality of life myeloma module (EORTC QLQ-MY20) [ Time Frame: Baseline; up to approximately 4 years ]
    EORTC QLQ-MY20, a 20-item questionnaire is used to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with multiple myeloma.

  22. Change from baseline in the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) scores [ Time Frame: Baseline; up to approximately 4 years ]
    EQ-5D-5L questionnaire is a measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and visual analogue scale (VAS). The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the respondent's self-rated health on a 20 cm vertical, VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine.'

  23. Number of participants with chromosomal abnormalities [ Time Frame: Up to approximately 4 years ]
    Explore chromosomal abnormalities (mainly but not limited to t(4;14), t(14;16), del(17p), and 1q21+)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

-Participants with multiple myeloma who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor, and with measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours) and/or serum free light chain (FLC) assay (Involved FLC assay ≥10 mg/dL and abnormal serum FLC ratio (<0.26 or >1.65))

Exclusion Criteria:

  • Participants less than 18 years old, participants with Eastern Cooperative Oncology Group performance status more than 2
  • Primary refractory multiple myeloma participants
  • Participants refractory to anti-CD38 with a wash-out period inferior to 9 months or intolerant to anti-CD38 mAb agents
  • Prior therapy with pomalidomide
  • Participants with inadequate biological tests.
  • Significant cardiac dysfunction
  • Participants diagnosed or treated for another cancer within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low risk prostate cancer after curative therapy
  • Concomittant plasma cell leukemia
  • Active primary amyloid-light (AL) amyloidosis
  • Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment
  • Hepatitis A, B, or C active infection
  • Women of childbearing potential or male participant 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 participant'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): NCT05405166


Contacts
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Contact: Trial Transparency email recommended (Toll free for US & Canada) 800-633-1610 ext Option 6 Contact-US@sanofi.com

Locations
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Australia, New South Wales
Investigational Site Number :0360004 Recruiting
Waratah, New South Wales, Australia, 2298
Investigational Site Number :0360003 Recruiting
Wollongong, New South Wales, Australia, 2500
Australia, Victoria
Investigational Site Number :0360001 Recruiting
Richmond, Victoria, Australia, 3121
Chile
Investigational Site Number :1520002 Recruiting
Santiago, Reg Metropolitana De Santiago, Chile, 7500653
Investigational Site Number :1520003 Recruiting
Santiago, Reg Metropolitana De Santiago, Chile, 7500921
Investigational Site Number :1520001 Recruiting
Temuco, Chile, 4800827
Investigational Site Number :1520005 Recruiting
Viña Del Mar, Chile
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT05405166    
Other Study ID Numbers: EFC15951
U1111-1261-5846 ( Registry Identifier: ICTRP )
First Posted: June 6, 2022    Key Record Dates
Last Update Posted: September 2, 2022
Last Verified: September 1, 2022
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://vivli.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Pomalidomide
Antibodies, Monoclonal
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
Immunologic Factors
Angiogenesis Inhibitors