Etude : ANDROMEDA / 54767414AMY3001



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 : ANDROMEDA

Nom : 54767414AMY3001

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 22/10/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Randomized Phase 3 Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic AL Amyloidosis

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : Participant involved in study for approx. 8 years duration includes Screening Phase (complete clinical evaluation will be done), Treatment Phase (monitoring of adverse events (AEs), laboratory abnormalities and clinical response), Post-Treatment Observation Phase (disease evaluations will be done) and a Long-term Follow-up Phase (Subsequent anticancer treatment, response to subsequent treatment, date of progression and survival status will be obtained every 16 weeks).The primary hypothesis is that daratumumab in combination with CyBorD will improve the overall complete hematological response rate compared to CyBorD alone in AL amyloidosis participants. Safety will be assessed by AEs, laboratory test results, electrocardiogram, vital sign measurements, physical examination, and Eastern Cooperative Oncology Group (ECOG) performance status.

Study arms:
- Active Comparator: CyBorD alone (cyclophosphamide/bortezomib/dexamethasone)
Participants will receive dexamethasone (40 milligrams [mg] orally or intravenous [IV] dose), followed by cyclophosphamide (300 milligram per meter square [mg/m^2] orally or IV dose), then bortezomib (1.3 mg/m^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles.
Interventions:
* Drug: Cyclophosphamide, Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose.
* Drug: Bortezomib, Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection.
* Drug: Dexamethasone, 40 mg orally or IV dose

- Experimental: CyBorD plus Daratumumab
Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m^2 orally or IV dose weekly) and bortezomib (1.3 mg/m^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years.
Interventions:
* Drug: Cyclophosphamide, Participants will receive 300 mg/m^2 of cyclophosphamide as an oral or IV dose.
*Drug: Bortezomib, Participants will receive 1.3 mg/m^2 of bortezomib as an subcutaneous (SC) injection.
* Drug: Dexamethasone, 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg
* Drug: Daratumumab, Participants will receive 1800 mg of daratumumab subcutaneously.

Current primary outcome:
Percentage of Participants With Overall Complete Hematologic Response [ Time Frame: Approximately 3 years ]
Overall complete hematologic response rate will be defined as percentage of participants who achieve Complete Hematologic Response (CHR), according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum and urine immunofixation.

Current secondary outcomes:
- Major Organ Deterioration Progression-Free Survival (MOD-PFS) [ Time Frame: Approximately 5 years ]
- Progression-Free Survival (PFS) [ Time Frame: Approximately 5 years ]
- Organ Response Rate (OrRR) [ Time Frame: Approximately 5 years ]
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Fatigue Scale Score [ Time Frame: Baseline, up to end of study (approximately 5 years) ]
- Change From Baseline in the 36-Item Short Form Survey version 2 (SF-36v2) Mental Component Summary (MCS) [ Time Frame: Baseline, up to end of study (approximately 5 years) ]
- Change From Baseline in the EORTC QLQ-C30 Global Health Status Scale Score [ Time Frame: Baseline, up to end of study (approximately 5 years) ]
- Time to Next Treatment (TNT) [ Time Frame: Approximately 5 years ]
- Hematologic Very Good Partial Response or Better Rate [ Time Frame: Approximately 3 years ]
- Time to Complete Hematologic Response [ Time Frame: Approximately 3 years ]
- Time to Hematologic Very Good Partial Response (VGPR) or Better Response [ Time Frame: Approximately 3 years ]
- Duration of Complete Hematologic Response [ Time Frame: Approximately 5 years ]
- Duration of Hematologic Very Good Partial Response (VGPR) or Better Response [ Time Frame: Approximately 5 years ]
- Time to Organ Response [ Time Frame: Approximately 5 years ]
- Duration of Organ Response [ Time Frame: Approximately 5 years ]

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 : - Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance
- Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:
* serum monoclonal (M)-protein greater than or equal (>=) 0.5 grams/deciliter (g/dL) by protein electrophoresis (routine serum protein electrophoresis and immunofixation [IFE] performed at a central laboratory)
* serum free light chain greater than or equal to (>=) 50 milligram/Liter (mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L
- One or more organs impacted by AL amyloidosis according to consensus guidelines
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2

Critères de non-inclusion : - Prior therapy for AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to randomization
- Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >= 60 percent (%) plasma cells in the bone marrow, or hypercalcemia
- Evidence of significant cardiovascular conditions as specified below:
* NT-ProBNP > 8500 nanogram per liter (ng/L)
* New York Heart Association (NYHA) classification IIIB or IV heart failure
* Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
* Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months
* For participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
* Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators [ICD] is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study)
* Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc interval
* Supine systolic blood pressure < 90 millimeter of mercury (mmHg), or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 20 mmHg despite medical management (eg, midodrine, fludrocortisones) in the absence of volume depletion
- Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted
- Known to be seropositive for human immunodeficiency virus (HIV)
- Any one of the following:
* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
* Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
- Grade 2 sensory or Grade 1 painful peripheral neuropathy
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03201965
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 :
Docteur Salomon Manier

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

Ouverture de l'essai : CLOS

MAJ : 22/10/2019