Etude : MS201814_0010 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : MS201814_0010

Situation thérapeutique : Induction

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 03/12/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase I Open Label First in Human Dose Escalation of the Immunoproteasome Inhibitor M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone in Participants With Relapsed Refractory Multiple Myeloma

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C90 - Myélome multiple et tumeurs malignes à plasmocytes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The purpose of this study is to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and early efficacy signs of M3258 as a single agent and co-administered with dexamethasone in participants with Relapsed Refractory Multiple Myeloma (RRMM).

STUDY ARMS:
- Experimental: Part A (Dose Escalation): M3258
Participants will receive M3258 in a protocol-defined dose escalation scheme in Part A
- Experimental: Part B (Dose Expansion): M3258
Participants will receive M3258 at a dose and regimen defined and considered to be safe by safety monitoring committee (SMC) in Part B until disease progression.
Participants will receive dexamethasone at a cumulative dose of 40 milligrams per week along with M3258 in Part B until disease progression.

CURRENT PRIMARY OUTCOME:
Part A and Part B:
- Number of Participants with Dose-Limiting Toxicity (DLTs) [ Time Frame: Day 1 up to Day 28 of Treatment Cycle 1 (each cycle is of 28 days) ]
- Occurrences of Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs ) [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]
-Number of Participants With Treatment Emergent Changes From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status, Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]

Part A:
- Number of Participants with Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLTs) Period [ Time Frame: Day 29 upto 30 days post-last dose (assessed upto maximum 528 days) ]

Part B:
- Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Duration of Response (DOR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Occurrence of Study Treatment-Emergent SAEs Including Deaths [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]

CURRENT SECONDARY OUTCOMES:
Part A:
-Maximum Observed Plasma Concentration (Cmax) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose upto 24 hours post-dose, Day 8 Cycle 1: Pre-dose upto 8 hours post-dose (each Cycle is of 28 days) ]
- Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC 0-t) of M3258 [ Time Frame: Pre-dose upto 24 hours post-dose on Day 1 of Cycle 1 (each cycle is of 28 days) ]
- Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose upto 24 hours post-dose, Day 8 Cycle 1: Pre-dose upto 8 hours post-dose (each Cycle is of 28 days) ]
- Change in Large Multifunctional Protease 7 (LMP7) Activity as Assessed by LMP7 Activity Assay [ Time Frame: Pre-dose, 2, 6 hours post-dose on Day 1 and Day 8 of Cycle 1; Pre-dose on Day 2 of Cycle 1 (each cycle is of 28 days) ]
- Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Change From Baseline in Urine M-protein Level Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Change From Baseline in Free Light Chain Protein Level Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Duration of Response (DOR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]

Part B:
- Progression-Free Survival (PFS) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Overall Survival Time According to International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Maximum Observed Plasma Concentration (Cmax) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose; Day 8 Cycle 1: pre-dose, 2, 4, and 6 hours post-dose (each cycle is of 28 days) ]
- Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC 0-t) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose (each cycle is of 28 days) ]
- Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose; Day 8 Cycle 1: pre-dose, 2, 4, and 6 hours post-dose (each cycle is of 28 days) ]

Phase : I

Stade : NA

Rechute, Réfractaire
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Participants having Eastern Co-operative Oncology Group (ECOG) Performance Status less than or equals to (<=) 1
- Adequate hematological, hepatic and renal function as defined in the protocol
- Participant must have measurable disease of Multiple Myeloma (MM) and received greater than (>) 3 prior lines of therapy for MM including a Proteasome Inhibitors (PI), an Immunomodulatory Imide Drug (IMiD) and an anti-CD38 mAb or who are refractory to at least PI agent (carfilzomib or bortezomib) and IMiD according to the International Myeloma Working Group (IMWG) criteria
- Participant must have documented evidence progressive disease as defined by the IMWG criteria either on or after their last regimen

--- Other protocol defined inclusion criteria could apply ---

Critères de non-inclusion : - Any condition, including any uncontrolled disease state that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
- An active second malignancy or evidence of disease of cancer (other than MM) before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
- Cerebrovascular accident/stroke (< 6 months prior enrollment) or neurologic instability per clinical evaluation due to tumor involvement of the Central Nervous System
- Diagnosis of fever within 1 week prior to study intervention administration
- Part B: Participants planning to undergo a stem cell transplant should not be enrolled to reduce disease burden prior to transplant.

--- Other protocol defined exclusion criteria could apply ---
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04075721
Promoteur :
EMD Serono Research & Development Institute, Inc.
Type de sponsor : Industriel
-
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Docteur Salomon Manier

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Statut de l'essai : CLOS

MAJ : 21/06/2021