SC versus IV isatuximab in combination with pomalidomide and dexamethasone in RRMM

JRCT ID: jRCT2031220425

Registered date:29/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Plasma cell myeloma recurrent
• Date of first enrollment: 01/11/2022
• Target sample size: 534
• Countries of recruitment: Australia,Japan,Chile,Japan
• Study type: Interventional

Intervention(s)

Drug: Isatuximab SC
Pharmaceutical form: Solution for subcutaneous administration, Route of administration: Subcutaneous (SC), Other Name: SAR650984

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

Outcome(s)

Primary Outcome

1. Overall response rate (ORR)
[Time frame for evaluation: 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 for evaluation: Predose at Cycle 6 Day 1 (duration of each cycle is 28 days)]
Observed Isatuximab plasma concentration.

Secondary Outcome

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: *]
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: *]
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: *]
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: *]
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: *]
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: *]
Maximum plasma concentration (Cmax)
13. PK parameter [Time Frame: *]
Area under the plasma concentration time curve over the dosing period (AUC)
14. Successful injection rate [Time Frame: *]
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: *]
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.
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]
23. Number of participants with chromosomal abnormalities [Time Frame: *]
Explore chromosomal abnormalities (mainly but not limited to t(4;14), t(14;16), del(17p), and 1q21+)
* #3, 8-15, 23: [Time Frame: Up to approximately 4 years]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both
• Include 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))

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05405166