BELUMOSUDIL MESILATE for Multiple myeloma (relapsed or refractory) | Plasma cell myeloma refractory

Inclusion criteria

• {"criterion_text":"- Participant must be 18 years of age inclusive or older."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status 0-1."}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- RRMM with measurable disease: Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or"}
• {"criterion_text":"- RRMM with measurable disease: Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Men or woman or childbearing potential should agree to use contraception"}
• {"criterion_text":"- Substudy 05: Participants with RRMM with at least 1 cycle of prior exposure to anti- CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory"}

Exclusion criteria

• {"criterion_text":"- Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma."}
• {"criterion_text":"- Uncontrolled infection within 14 days prior to first study intervention administration."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A."}
• {"criterion_text":"- Uncontrolled or active hepatitis B virus (HBV) infection."}
• {"criterion_text":"- Active hepatitis C virus (HCV) infection."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone."}
• {"criterion_text":"- Participants with a contraindication to treatment."}
• {"criterion_text":"- Vaccination with a live vaccine 4 weeks before the start of the study."}
• {"criterion_text":"- Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted."}
• {"criterion_text":"- Hemoglobin <8 g/dL."}
• {"criterion_text":"- Platelets <50 × 10^9/L."}
• {"criterion_text":"- Absolute neutrophil count <1.0 × 10^9/L."}
• {"criterion_text":"- Creatinine clearance <30 mL/min/1.73m2."}
• {"criterion_text":"- Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN."}
• {"criterion_text":"- Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN."}
• {"criterion_text":"- Patients with grade 3 or 4 hypercalcemia"}
• {"criterion_text":"- Substudy 05:Unable to swallow tablets."}

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 part to determine or confirm the recommended dose of novel agents when combined with isatuximab; specific dose-escalation rules or measurement metrics not provided in metadata."}
• {"endpoint_text":"- Part 2 (expansion, independent experimental substudies):Overall Response Rate (ORR) in independent experimental substudies","definition_or_measurement_approach":"ORR (overall response rate) measured in independent experimental substudies; specific response criteria not detailed in metadata."}

Secondary endpoints

• {"endpoint_text":"- Part 1 (dose finding, experimental substudies): ORR","definition_or_measurement_approach":"Overall Response Rate in Part 1; specific measurement criteria not provided."}
• {"endpoint_text":"- Part 1 (dose finding, experimental substudies): VGPR or better","definition_or_measurement_approach":"Very Good Partial Response (VGPR) or better; specific definitions not provided in metadata."}
• {"endpoint_text":"- Part 2 (expansion, independent experimental substudies): VGPR or better","definition_or_measurement_approach":"VGPR or better in Part 2; specific definitions not provided in metadata."}
• {"endpoint_text":"- Clinical Benefit Rate (CBR) in each treatment arm","definition_or_measurement_approach":"Clinical Benefit Rate assessed per treatment arm; exact definition not provided in metadata."}
• {"endpoint_text":"- Duration of Response (DOR) in each treatment arm","definition_or_measurement_approach":"Duration of Response measured per arm; exact calculation not provided in metadata."}
• {"endpoint_text":"- Time to First Response (TT1R) in each treatment arm","definition_or_measurement_approach":"Time from treatment start to first documented response per arm; precise censoring rules not provided."}
• {"endpoint_text":"- Time to Best Response (TTBR) in each treatment arm","definition_or_measurement_approach":"Time to best observed response per arm; detailed measurement not provided."}
• {"endpoint_text":"- Number of participants with treatment emergent adverse events and serious adverse events in each treatment arm","definition_or_measurement_approach":"Count of participants with TEAEs and SAEs per arm; standard collection of AEs/SAEs implied but not specified in metadata."}
• {"endpoint_text":"- Progression-free survival (PFS) in each treatment arm","definition_or_measurement_approach":"PFS assessed per arm; specific assessment schedule not provided in metadata."}
• {"endpoint_text":"- Overall Survival (OS) in each treatment arm","definition_or_measurement_approach":"OS measured per arm; details not provided in metadata."}
• {"endpoint_text":"- Immunogenicity of isatuximab and novel agents","definition_or_measurement_approach":"Assessment of potential immunogenicity of isatuximab and novel agents when applicable; assay details not provided."}
• {"endpoint_text":"- Concentration of novel agents (experimental arms) and isatuximab (Ctrough)","definition_or_measurement_approach":"Ctrough concentrations measured for isatuximab and novel agents; sampling schedule not provided."}
• {"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":"HRQL assessed using EORTC QLQ-C30 questionnaire."}
• {"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":"HRQL assessed using EORTC QLQ-MY20 module."}
• {"endpoint_text":"- Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)","definition_or_measurement_approach":"Global impact of side effects assessed using FACT-G (GP5)."}
• {"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 PGIS and PGIC scales to estimate/confirm clinically meaningful change scores for COAs/domain scores."}
• {"endpoint_text":"- Maximum concentration observed after the first infusion (Cmax) for Belumosudil - Substudy 05","definition_or_measurement_approach":"Cmax measured after first infusion for Belumosudil in Substudy 05."}
• {"endpoint_text":"- Time to reach Cmax (tmax) for Belumosudil - Substudy 05","definition_or_measurement_approach":"tmax measured for Belumosudil in Substudy 05."}
• {"endpoint_text":"- Area under the concentration versus time curve calculated using the trapezoidal method from 0 to 8h (AUC0-8h) for Belumosudil - Substudy 05","definition_or_measurement_approach":"AUC0-8h for Belumosudil calculated using trapezoidal method (0–8 h) in Substudy 05."}

France

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

487

Number Of Sites

4

Number Of Participants

3

Portugal

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

487

Number Of Sites

2

Number Of Participants

2

Norway

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

490

Number Of Sites

1

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

488

Number Of Sites

2

Number Of Participants

3

Greece

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

489

Number Of Sites

2

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

591

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Endpoint Clinical Inc.

Third parties

• {"country":"Australia","full_name":"Cellcarta Pty Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta Biosciences","duties_or_roles":"","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":"Azenta US Inc.","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}