Etude : CEPHEUS / 54767414MMY3019



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : CEPHEUS

Nom : 54767414MMY3019

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 03/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

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 to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.

Study arms:
- Active Comparator: Bortezomib + Lenalidomide + Dexamethasone (VRd) and Rd
Participants will receive bortezomib 1.3 milligram per square meter (mg/m^2) as subcutaneous (SC) injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 (cycle of 28 days); dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond (each cycle is of 28 days) followed by lenalidomide-dexamethasone (Rd) until disease progression or unacceptable toxicity.
Interventions:
Drug: Bortezomib
Drug: Lenalidomide
Drug: Dexamethasone
- Experimental: Daratumumab + VRd (D-VRd) and DRd
Participants will receive daratumumab 1800 mg as SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3 through 8 and every 4 weeks for Cycle 9 and beyond; bortezomib 1.3 mg/m^2 as SC injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9; dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond followed by daratumumab-lenalidomide-dexamethasone (DRd) until disease progression or unacceptable toxicity.
Interventions:
Drug: Daratumumab
Drug: Bortezomib
Drug: Lenalidomide
Drug: Dexamethasone


Current primary outcome:
Percentage of Participants with Negative Minimal Residual Disease (MRD) Status [ Time Frame: After randomization and prior to progressive disease (PD) or subsequent anti-myeloma therapy approximately 2.5 years ]

Current secondary outcomes:
- Progression-Free Survival (PFS) [ Time Frame: From randomization to either disease progression or death whichever occurs first (approximately 6 years, or 9 years if the adaptive approach is decided at the interim) ]
- MRD Negative Rate at 1 Year [ Time Frame: 1 year after last participant first dose (approximately 2.5 year) ]
- Durable MRD Negative Rate [ Time Frame: Throughout the study (approximately 6 year) ]
- Overall Response Rate (ORR) [ Time Frame: Up to the end of the study (approximately 6 years) ]
- Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Approximately 6 years ]
- Complete Response (CR) or Better Rate [ Time Frame: Approximately 6 years ]
- PFS on the Next Line of Therapy [ Time Frame: Time from randomization to progression on the next line of treatment or death, whichever comes first (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim) ]
- Overall Survival (OS) [ Time Frame: From randomization until the participant's death from any cause (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim) ]
- Time to Response [ Time Frame: From randomization until PR or better until approximately 6 years ]
- Duration of Response (DOR) [ Time Frame: From initial documentation of response to the date of PD until approximately 6 years ]
- Change from Baseline in Health-related Quality of Life (HRQoL) using EORTC Questionnaires [ Time Frame: Up to approximately 6 years ]
- Change from Baseline in Health-related Quality of Life (HRQoL) using EQ-5D-5L Questionnaire [ Time Frame: Up to approximately 6 years ]
- Maximum Observed Serum Concentration (Cmax) of Daratumumab [ Time Frame: Predose Cycle 1, Day 1 (C1D1), C3D1, C9D1, C12D1, and post dose C1D4, C3D4, Post-treatment Week 8 (Cycle 1 to 8 is of 21 days; Cycle 9 and onwards are of 28 days) ]
- Minimum Observed Serum Concentration (Cmin) of Daratumumab [ Time Frame: Predose, C1D1 (each cycle of 28 days), C3D1, C9D1, C12D1, and post dose C1D4, C3D4, Post-treatment Week 8 (Cycle 1 to 8 is of 21 days; Cycle 9 and onwards are of 28 days) ]
- Number of Participants with Anit-daratumumab Antibodies [ Time Frame: Predose, C1D1 (each cycle of 28 days), C9D1, C12D1, Post-treatment Week 8 (Cycle 1 to 8 is of 21 days; Cycle 9 and onwards are of 28 days) ]
- Number of Participants with Anit-rHuPH20 Antibodies [ Time Frame: Predose, C1D1 (each cycle of 28 days), C9D1, C12D1, Post-treatment Week 8 (Cycle 1 to 8 is of 21 days; Cycle 9 and onwards are of 28 days) ]

Phase : III

Stade : NA

NA
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 : - Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria Monoclonal plasma cells in the bone marrow greater than or equal to (>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria.
* CRAB criteria: Hypercalcemia: serum calcium greater than (>) 0.25 millimoles per liter (mmol/L) (>1 milligram per deciliter [mg/dL]) higher than upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL); Renal insufficiency: creatinine clearance less than (<) 40 milliliter per minute (mL/min) or serum creatinine >177 micro millimoles per liter (umol/L) (>2 mg/dL); Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.
* Biomarkers of Malignancy: Clonal bone marrow plasma cell percentage >=60%; Involved: uninvolved serum free light chain (FLC) ratio >=100; >1 focal lesion on magnetic resonance imaging (MRI) studies
- Must have measurable disease, as assessed by central laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing
- A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen

Critères de non-inclusion : - Frailty index of >=2 according to Myeloma Geriatric Assessment score
- Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days, total of 160 mg dexamethasone or equivalent)
- Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion 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)
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
- Radiation therapy within 14 days of randomization
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03652064
Promoteur :
JANSSEN
Type de sponsor : Industriel
JANSSEN - JANSSEN
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 :
Professeur Thierry FACON

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

Ouverture de l'essai : OUVERT

MAJ : 08/07/2019