A Study to Evaluate the Effectiveness and Safety of CAEL-101 in Patients with Mayo Stage IIIa AL Amyloidosis

Overview

About this study

The purpose of this study is to determine if CAEL-101 improves the overall survival in patients with cardiac AL Amyloidosis.

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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:

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/Immunofluroescence

2. Mass spectrometry or

3. 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/29/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Angela Dispenzieri, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Craig Reeder, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Taimur Sher, M.B.B.S., M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
.

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