Etude : CAEL101-301 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : CAEL101-301

Situation thérapeutique : Induction

Traitement :

Cadre réglementaire : RIPH1

Dernière MÀJ : 30/11/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 3, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of CAEL-101 and Plasma Cell Dyscrasia Treatment Versus Placebo and Plasma Cell Dyscrasia Treatment in Plasma Cell Dyscrasia Treatment-Naïve Patients with Mayo Stage IIIb 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 : This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101 combined with the standard of care (SoC) for plasma cell dyscrasia (PCD) versus placebo combined with standard of care PCD treatment in patients with Mayo stage IIIb AL amyloidosis that have not received prior treatment. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient's death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment.

Approximately 111 patients will be enrolled using a 2:1 randomization ratio of CAEL-101: placebo and will involve approximately 70 investigator sites.

The primary objective of this study is to assess the effects of CAEL-101 versus placebo on all-cause mortality.

STUDY ARMS:
- Experimental: CAEL-101 combined with SoC plasma cell dyscrasia
CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The minimum planned treatment time for each patient will be at least 50 weeks or until the patient's death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 54 deaths have been observed.
Interventions:
Drug: CAEL-101
Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

- Placebo Comparator: Placebo combined with SoC plasma cell dyscrasia
Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). The minimum planned treatment time for each patient will be at least 50 weeks or until the patient's death. It is planned that all patients will continue their double-blind treatment until the last patient completes at least 50 weeks of treatment. As this is an event driven study, the study will continue, and all patients will continue to receive study treatment until at least 54 deaths have been observed.
Interventions:
Other: Placebo
Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

- Concurrent Plasma Cell Dyscrasia Treatment
All patients will also receive concurrent treatment for Plasma Cell Dyscrasia (PCD) according to institutional SoC. Patients will have a planned first-line PCD treatment with a CyBorD regimen according to institutional SoC and initiate their PCD treatment within 7 days of receiving the first dose of study drug. Patients can refer to the package insert or Summary of Product Characteristics (SmPC) for contraindications, warnings and precautions for PCD medications.

PRIMARY OBJECTIVES:
• To determine if CAEL-101 and treatment for plasma cell dyscrasia improves overall survival in Mayo stage IIIb AL amyloidosis patients who are treatment naïve compared to treatment for plasma cell dyscrasia alone
• To evaluate the safety and tolerability of CAEL-101 in combination with treatment for plasma cell dyscrasia

KEY SECONDARY OBJECTIVES:
• To assess functional improvement as measured by the distance walked in the six-minute walk test (6MWT)
• To assess quality of life as measured by the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)
• To assess quality of life as measured by the Short Form 36 version 2 Physical Component Score (SF-36v2® PCS)
• To assess cardiac improvement as measured by percent Global Longitudinal Strain (GLS%)

Phase : III

Stade : NA

1 (hémato)
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 : - Be able to and provide written informed consent and be willing and able to comply with all study procedures
- Adult, 18 years and older
- AL amyloidosis Mayo stage IIIb based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement at the time of Screening
- Measurable hematologic disease at Screening as defined by at least one of the following:
*Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or
*Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or
*Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL

- Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid deposits by at least one of the following:
*Immunohistochemistry or
*Mass spectrometry or
*Characteristic electron microscopy appearance

- Cardiac involvement as defined by:
*Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND
*At least one of the following:
i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or
ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening or
iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis
- Planned first-line treatment for plasma cell disorder is a CyBorD-based regimen administered as Standard of Care (SoC)
- Adequate bone marrow reserve and hepatic function as demonstrated by:
*Absolute neutrophil count ≥ 1.0 x 109/L
*Platelet count ≥ 75 x 109/L
*Hemoglobin ≥ 9 g/dL
*Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless due to Gilbert's syndrome.
*Aspartate aminotransferase (AST) ≤ 3 x ULN
*Alanine aminotransferase (ALT) ≤ 3 x ULN
*Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone)

- Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician approved contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer
- Men must be surgically sterile or must agree to use effective physician approved contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of his PCD therapy, whichever is longer.

Critères de non-inclusion : - Have any other form of amyloidosis other than AL amyloidosis
- Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL amyloidosis and prior to randomization is allowed.
- Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma or POEMS syndrome
- Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
- Taking prednisone or its equivalent > 10 mg/day
- Taking doxycycline
- Receiving dialysis
- Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted.
- Have had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor.
- Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening
- Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2) or severe congenital heart disease
- Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Participants who do have a pacemaker or ICD are allowed in the study.)
- QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval.
- There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
*First degree Atrioventricular (AV)-block
*Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)
*Right or left bundle branch block
*Atrial fibrillation with a controlled ventricular rate. (An uncontrolled ventricular rate [i.e., > 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed)
- Have had major surgery within 4 weeks of randomization or is planning major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate
-There is active malignancy (including lymphoma) with the exception of any of the following:
*Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
*Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years
*Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL
*Other localized and/or low risk malignancies may be permitted with Medical Monitor approval.
- Have received an investigational drug/device in another clinical investigational study within 60 days before Screening
- Hypersensitivity to the study drug
- Have received a live vaccine within 4 weeks prior to first dose of CyBorD
- Women who are breast feeding
- Have any other medical, social or psychological factors that could affect the patient's safety or ability to consent personally or comply with study procedures.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04504825
Promoteur :
CAELUM BIOSCIENCES
Type de sponsor : Industriel
USA - USA
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 : OUVERT

MAJ : 01/07/2021