Multiple Myeloma Clinical Trial
A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis
Summary
AL (or light chain) amyloidosis begins in the bone marrow where abnormal proteins misfold and create free light chains that cannot be broken down. These free light chains bind together to form amyloid fibrils that build up in the extracellular space of organs, affecting the kidneys, heart, liver, spleen, nervous system and digestive tract.
The primary purpose of this study is to determine whether CAEL-101, a monoclonal antibody that removes AL amyloid deposits from tissues and organs, improves overall survival and it is safe and well tolerated in patients with stage IIIa AL amyloidosis.
Full Description
This is a double-blind, randomized, multicenter international Phase 3 study of CAEL-101 combined with standard of care (SoC) plasma cell dyscrasia (PCD) treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIa PCD treatment-naïve AL amyloidosis patients. As this is an event-driven study, the study will enroll until at least 79 deaths have been observed. Approximately 267 patients will be enrolled using a 2:1 randomization ratio. An interim analysis (IA) may also be performed when at least 75% of the events have been observed. Patients in both study intervention groups will be followed from randomization until death from any cause or until the end of study.
Eligibility Criteria
Key Inclusion Criteria:
AL amyloidosis stage IIIa based on the European Modification of the 2004 Standard Mayo Clinic Staging who also have NT-proBNP > 650 ng/L 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 Kappa/Lambda ratio or
Serum protein electrophoresis (SPEP) m-spike > 0.5 g/dL
Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following:
Immunohistochemistry/Immunofluroescence
Mass spectrometry or
Characteristic electron microscopy appearance/Immunoelectron microscopy
Cardiac involvement as defined by:
a. 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 b. 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 magnetic resonance imaging (MRI) with gadolinium contrast agent diagnostic of cardiac amyloidosis
Planned first-line treatment for plasma cell dyscrasia is a cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC
Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective 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 highly effective contraception 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
Key Exclusion Criteria:
Have any other form of amyloidosis other than AL amyloidosis
Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples are obtained and prior to randomization is allowed.
Has POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) syndrome or multiple myeloma defined as clonal bone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months prior to signing the ICF) or biopsy-proven (performed ≤ 3 months prior to signing the ICF) bony or extramedullary plasmacytoma AND one or more of the following CRAB features:
a. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal (ULN) or > 2.75 mmol/L (> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 mol/L (> 2 mg/dL) OR iii. Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L OR iv. Bone lesions: one or more osteolytic lesion on imaging tests (performed ≤ 3 months prior to signing the ICF): skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT, or MRI. If bone marrow has < 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement OR b. Any one of the following biomarkers of malignancy: i. 60% or greater clonal plasma cells on bone marrow examination OR ii. More than one focal lesion on MRI that is at least 5 mm or greater in size
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
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There are 122 Locations for this study
Phoenix Arizona, 85054, United States
Scottsdale Arizona, 85054, United States
Duarte California, 91010, United States
Palo Alto California, 94305, United States
San Francisco California, 94143, United States
Jacksonville Florida, 32224, United States
Weston Florida, 33331, United States
Indianapolis Indiana, 46202, United States
New Orleans Louisiana, 70112, United States
Baltimore Maryland, 21201, United States
Boston Massachusetts, 02111, United States
Boston Massachusetts, 02115, United States
Boston Massachusetts, 02118, United States
Detroit Michigan, 48201, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
New York New York, 10021, United States
New York New York, 10032, United States
New York New York, 10065, United States
Rochester New York, 14642, United States
Chapel Hill North Carolina, 27599, United States
Durham North Carolina, 27705, United States
Winston-Salem North Carolina, 27157, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43210, United States
Portland Oregon, 97239, United States
Philadelphia Pennsylvania, 19104, United States
Pittsburgh Pennsylvania, 15232, United States
Charleston South Carolina, 29425, United States
Nashville Tennessee, 37232, United States
Dallas Texas, 75390, United States
Houston Texas, 77030, United States
Salt Lake City Utah, 84112, United States
Seattle Washington, 98109, United States
Madison Wisconsin, 53792, United States
Milwaukee Wisconsin, 53226, United States
Adelaide , SA 50, Australia
Box Hill , VIC 3, Australia
Brisbane , QLD 4, Australia
Murdoch , WA 61, Australia
Sydney , NSW 2, Australia
Linz , 1090, Austria
Linz , 4020, Austria
Bruxelles , 1000, Belgium
Bruxelles , 1200, Belgium
Leuven , 3000, Belgium
Porto Alegre , 90110, Brazil
Recife , 50040, Brazil
Ribeirao Preto , 14051, Brazil
Santo Amaro , 50040, Brazil
Sao Jose do Rio Preto , 15090, Brazil
Sao Paulo , 05652, Brazil
São Paulo , 41253, Brazil
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 1, Canada
Toronto Ontario, M5G 2, Canada
Beijing , 10073, China
Guangzhou , 51031, China
Hangzhou , 31000, China
Wenzhou , 32501, China
Ostrava , , Czechia
Caen , 14033, France
Créteil , 94010, France
Dijon , 21079, France
Lille , 59037, France
Limoges , 87042, France
Marseille , 13009, France
Paris , 75010, France
Pessac , 33604, France
Pierre-Bénite , 69310, France
Poitiers , 86021, France
Rennes , 35033, France
Tours , 37000, France
Berlin , 12203, Germany
Dusseldorf , 40225, Germany
Essen , 45417, Germany
Hamburg , 22767, Germany
Heidelberg , 69120, Germany
Mainz , 55131, Germany
Münster , 48149, Germany
Würzburg , 97080, Germany
Athens , 11528, Greece
Patras , 26504, Greece
ThessalonÃki , 546 3, Greece
Haifa , 31999, Israel
Jerusalem , 91120, Israel
Petach Tikva , 49414, Israel
Tel Aviv , 64239, Israel
Tel-Hashomer , , Israel
Brescia , 25123, Italy
Naples , 80131, Italy
Pavia , 27100, Italy
Rome , 00128, Italy
Kumamoto-shi Kumamoto, 860-8, Japan
Chiba , 277-8, Japan
Fukushima , 960-1, Japan
Ishikawa , 920-8, Japan
Kyoto , 603-8, Japan
Nagoya , 467-8, Japan
Tokyo , 150-8, Japan
Seoul , 3080, Korea, Republic of
Seoul , 3722, Korea, Republic of
Seoul , 6351, Korea, Republic of
Seoul , 6591, Korea, Republic of
Amsterdam , 1105, Netherlands
Groningen , 9713, Netherlands
The Hague , 2545, Netherlands
Gdansk , 80-21, Poland
Poznan , 60-56, Poland
Warsaw , 02-09, Poland
Saint Petersburg , 19702, Russian Federation
Saint Petersburg , 19734, Russian Federation
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Gijon , 33203, Spain
Granada , 18014, Spain
Madrid , 28003, Spain
Madrid , 28040, Spain
Madrid , 28222, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
Sevilla , 41013, Spain
Valencia , 46009, Spain
Glasgow , G12 0, United Kingdom
London , NW1 2, United Kingdom
London , NW1 2, United Kingdom
London , NW3 2, United Kingdom
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