ISATUXIMAB for Multiple myeloma|Relapsed or refractory multiple myeloma (RRMM)

Inclusion criteria

• {"criterion_text":"- Participant must be 18 years of age inclusive or older\n- Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n- Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line).\n- RRMM with measurable disease: Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or\n- RRMM with measurable disease: Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or\n- RRMM with measurable disease: Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio <0.26 or >1.65)\n- Men or woman or childbearing potential should agree to use contraception.\n- Substudy 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 12 months after the last dose. “Exposure” is defined as at least 2 cycles of therapy."}

Exclusion criteria

• {"criterion_text":"- Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma\n- Participants with a contraindication to treatment.\n- Vaccination with a live vaccine 4 weeks before the start of the study.\n- Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.\n- Hemoglobin <8 g/dL.\n- Platelets <50 × 10^9/L.\n- Absolute neutrophil count <1.0 × 10^9/L.\n- Creatinine clearance <30 mL/min/1.73m2.\n- Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN\n- Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN.\n- Patients with grade 3 or 4 hypercalcemia.\n- Uncontrolled infection within 14 days prior to first study intervention administration.\n- Substudy 06:History of active autoimmune disorders.\n- Substudy 06:History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.\n- Substudy 06:Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD.\n- Substudy 06:Prior allogenic hematopoietic stem cell transplant (allo-HSCT).\n- Substudy 06:Participants with chronic active EBV infection.\n- Substudy 06:Participants with known history of HLH.\n- Substudy 06:Hemoglobin < 9 g/dL.\n- Substudy 06:Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent.\n- Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction <40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).\n- Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.\n- Uncontrolled or active hepatitis B virus (HBV) infection.\n- Active hepatitis C virus (HCV) infection.\n- Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.\n- Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration.\n- Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone"}

Primary endpoints

• {"endpoint_text":"- Part 1 (dose finding, experimental substudies): Determination of recommended dose of novel agents in combination with isatuximab","definition_or_measurement_approach":"Dose-finding in Part 1 to determine or confirm the recommended dose of novel agents when combined with isatuximab (measurement: dose-escalation/determination procedures in Part 1; specific rules not provided in the record)."}
• {"endpoint_text":"- Part 2 (expansion, controlled experimental substudies): VGPR Rate (Rate of Very Good Partial Response Rate or Better)","definition_or_measurement_approach":"Measurement: rate of very good partial response (VGPR) or better in Part 2 (VGPR rate assessed per response criteria; exact assessment criteria not detailed in the record)."}

Secondary endpoints

• {"endpoint_text":"- Part 1 (dose finding, controlled experimental substudies): ORR","definition_or_measurement_approach":"Overall response rate (ORR) in Part 1 (dose finding); assessed per study-defined response criteria."}
• {"endpoint_text":"- Part 2 (expansion, controlled experimental substudies): ORR","definition_or_measurement_approach":"Overall response rate (ORR) in Part 2 (expansion); assessed per study-defined response criteria."}
• {"endpoint_text":"- Part 1 (dose finding, experimental substudies): VGPR or better","definition_or_measurement_approach":"Rate of VGPR or better in Part 1; assessed per response criteria."}
• {"endpoint_text":"- Clinical Benefit Rate (CBR) in each treatment arm","definition_or_measurement_approach":"Clinical benefit rate measured per-arm; definition as specified in protocol (not detailed in record)."}
• {"endpoint_text":"- Duration of Response (DOR) in each treatment arm","definition_or_measurement_approach":"DOR measured per-arm from first response to progression or relapse."}
• {"endpoint_text":"- Time to First Response (TT1R) in each treatment arm","definition_or_measurement_approach":"Time from first dose to first observed response in each arm."}
• {"endpoint_text":"- Time to Best Response (TTBR) in each treatment arm","definition_or_measurement_approach":"Time from first dose to best observed response in each arm."}
• {"endpoint_text":"- Number of participants with treatment emergent adverse events and serious adverse events in each treatment arm","definition_or_measurement_approach":"Safety endpoint: count and categorization of treatment-emergent adverse events and serious adverse events per arm (per NCI CTCAE)."}
• {"endpoint_text":"- Progression-free survival (PFS) in each treatment arm","definition_or_measurement_approach":"PFS measured per-arm (time from randomization/enrolment to disease progression or death)."}
• {"endpoint_text":"- Overall Survival (OS) in each treatment arm","definition_or_measurement_approach":"OS measured per-arm (time from randomization/enrolment to death from any cause)."}
• {"endpoint_text":"- Immunogenicity of isatuximab and novel agents","definition_or_measurement_approach":"Assessment of anti-drug antibodies and immunogenicity of isatuximab and novel agents when applicable."}
• {"endpoint_text":"- Concentration of novel agents (experimental arms) and isatuximab (Ctrough)","definition_or_measurement_approach":"PK measurement: trough concentrations (Ctrough) of isatuximab and concentrations of novel agents in experimental arms."}
• {"endpoint_text":"- Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)","definition_or_measurement_approach":"Patient-reported outcome: EORTC QLQ-C30 to assess disease-specific health-related quality of life."}
• {"endpoint_text":"- Disease and treatment-related quality of life will be assessed using the EORTC multiple myeloma module (QLQ-MY20) questionnaire","definition_or_measurement_approach":"Patient-reported outcome: EORTC QLQ-MY20 module for multiple myeloma-specific QoL."}
• {"endpoint_text":"- Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)","definition_or_measurement_approach":"Assessment of global impact of side effects using FACT-G GP5 item."}
• {"endpoint_text":"- Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales","definition_or_measurement_approach":"Use of PGIS and PGIC to estimate/confirm clinically meaningful change scores for COAs/domain scores."}
• {"endpoint_text":"- Time to reach Cmax (tmax) for Evorpacept – Substudy 06","definition_or_measurement_approach":"PK parameter: time to maximum concentration (tmax) for evorpacept in Substudy 06."}
• {"endpoint_text":"- Time to reach Cmax (tmax) for Evorpacept – Substudy 06","definition_or_measurement_approach":"PK parameter: time to maximum concentration (tmax) for evorpacept in Substudy 06."}
• {"endpoint_text":"- Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval for evorpacept (AUC0-t)- Substudy 06","definition_or_measurement_approach":"PK parameter: AUC0-t for evorpacept calculated using trapezoidal method in Substudy 06."}

Methods

• K1 recruitment arrangements documents (multiple language versions) describing recruitment approach (documents present for multiple countries/languages).
• Doctor-to-doctor referral letters (K2 recruitment material; example: dr-to-dr-referral-letter-it) — channel: clinician referral; country-specific: Italy.
• Participant-facing leaflets/materials (e.g., urine collection leaflet K2 for France) and other recruitment leaflets — channel: patient information leaflets; country-specific examples include France.

France

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

17-10-2024

Processing Time Days

27

Number Of Sites

4

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

11-10-2024

Processing Time Days

21

Number Of Sites

2

Number Of Participants

2

Greece

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

24-10-2024

Processing Time Days

34

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

16-10-2024

Processing Time Days

26

Number Of Sites

2

Number Of Participants

4

Portugal

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

15-10-2024

Processing Time Days

25

Number Of Sites

2

Number Of Participants

2

Norway

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

16-10-2024

Processing Time Days

26

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Endpoint Clinical Inc.

Responsibilities

code 3

Third parties

• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Cellcarta Pty Limited","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"code 15 (sample storage)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta Biosciences","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"code 15 (sample storage)","organisation_type":"Pharmaceutical company"}