A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis

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Trial ID: NCT04504825

Purpose

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 IIIb AL amyloidosis.

Official Title

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

Stanford Investigator(s)

Michaela Liedtke
Michaela Liedtke

Associate Professor of Medicine (Hematology)

Eligibility


Key Inclusion Criteria:

   - AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo
   Clinic Staging (NT-proBNP > 8,500 ng/L) at the time of Screening

   - Measurable hematologic disease at Screening as defined by at least one of the
   following:

      1. Involved/uninvolved free light chain difference (dFLC) > 4 mg/dL or

      2. Involved free light chain (iFLC) > 4 mg/dL with abnormal Kappa/Lambda ratio or

      3. 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:

      1. Immunohistochemistry/Immunofluorescence or

      2. Mass spectrometry or

      3. Characteristic electron microscopy appearance/Immunoelectron microscopy

   - Cardiac involvement as defined by:

      1. 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

      2. 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
   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 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 their 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 (e.g., multiple myeloma and POEMS syndrome), specifically: i.
   Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the 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, CT, or 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 5mm 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

Intervention(s):

drug: CAEL-101

other: Placebo

drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Recruiting

I'm Interested

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Mani Gupta
650-723-0501

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