NCT04504825 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-02

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, reduces cardiovascular related hospitalizations and it is safe and well tolerated in patients with stage IIIb AL amyloidosis.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

A Hierarchical Combination of Time to All-cause Mortality and Frequency of Cardiovascular Hospitalizations (CVHs) Analyzed by Win Ratio

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)

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outcome · POSTED

Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT)

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outcome · POSTED

All-cause Mortality

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outcome · POSTED

Frequency of CVHs

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outcome · POSTED

Change From Baseline in Global Longitudinal Strain (GLS%)

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outcome · POSTED

Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS)

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outcome · POSTED

Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months. The study is divided into 2 parts, the Primary Evaluation Treatment period part and the Open-Label Extension period of Study.
intervention Names
Drug: CAEL-101
Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen
label
CAEL-101 combined with SoC plasma cell dyscrasia
type
EXPERIMENTAL
description
Patients randomized to receive placebo will receive 0.9% normal saline in an equivalent volume to a CAEL-101 infusion (approximately 250 cc). It is planned that all patients will continue their double-blind treatment until the last patient is randomized in the study plus 18 months.
intervention Names
Other: Placebo
Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen
label
Placebo combined with SoC plasma cell dyscrasia
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
CAEL-101 combined with SoC plasma cell dyscrasia
description
The investigational product, CAEL-101, is formulated as a sterile liquid solution of protein plus excipients for dilution in a single-use, stoppered, glass vial. Each 10 mL vial contains 300 mg of CAEL-101 at a concentration of 30 mg/mL. CAEL-101 will be diluted with commercially available 0.9% Normal Saline.
name
CAEL-101
type
DRUG
arm Group Labels
Placebo combined with SoC plasma cell dyscrasia
description
Commercially available 0.9% Normal Saline will be used as the placebo.
name
Placebo
type
OTHER
arm Group Labels
CAEL-101 combined with SoC plasma cell dyscrasia
Placebo combined with SoC plasma cell dyscrasia
description
According to institutional standard of care.
name
cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

This is a double-blind, randomized, multicenter, international Phase 3 study of CAEL-101 combined with SoC PCD treatment versus placebo combined with SoC PCD treatment in Mayo stage IIIb PCD treatment-naïve AL amyloidosis patients. Approximately 124 patients will be enrolled using a 2:1 randomization ratio and stratification will be based on geographic region across investigator sites. The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left valve assist device (LVAD) implantation or until the end of study.

masking Info

masking: QUADRUPLE
masking Description: This is a double-blind, randomized, multicenter international Phase 3 study.
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 125
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Time to all-cause mortality was defined as the number of weeks from the date of randomization to the date of death if it is on or before the end of PETP. Participants alive at the end of PETP (LPI+18 months) were censored at their last known alive date recorded within the PETP. CVHs were events adjudicated and confirmed as such by the Clinical Event Adjudication Committee (CEAC). Hypothesis testing with the Finkelstein-Schoenfeld test and treatment effect estimation with the win-ratio method based on pairwise comparisons of participant outcomes with comparisons performed in a hierarchical manner. To calculate win ratio, participant outcomes based on time to all-cause mortality were first compared and if there was no 'winner' due to censoring then a comparison based on frequency of cardiovascular hospitalization was made. A win ratio \>1 represents a more favorable outcome for CAEL-101 over placebo.
measure
A Hierarchical Combination of Time to All-cause Mortality and Frequency of Cardiovascular Hospitalizations (CVHs) Analyzed by Win Ratio
time Frame
Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.)
description
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, at any dose, that was not necessarily related to the treatment. A TEAE was an AE with an occurrence defined as follows: last study intervention day-first study intervention day + 140 days. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
time Frame
Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, the primary analysis for the study was conducted 18-47 months after the study randomization.)

secondary Outcomes

description
The KCCQ-OS is a 23-item self-administered questionnaire that quantifies physical function, symptoms, social function, self-efficacy and knowledge and quality of life. It uses an ordinal, adjectival (Likert) scale. Participants provide their level of agreement or disagreement with an agree-disagree scale for a series of statements. The questionnaire captures how the participants feel physically. The overall score was calculated as the sum from all 23 items and ranges from 0 to 100, where higher scores reflected better health status (fewer symptoms, fewer social or physical limitations, and better quality of life).
measure
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
time Frame
Baseline, Week 50
description
The 6MWT measures the distance a participant can quickly walk on a flat, hard surface in a period of 6 minutes. It evaluates the global and integrated response of all the systems involved during exercise. This is a self-paced test; participants choose their own intensity of exercise and are allowed to stop and rest during the test.
measure
Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT)
time Frame
Baseline, Week 50
description
All-cause mortality was defined as death on or before the end of the PETP. Participants who were alive at the end of the PETP (last participant randomized plus 18 months) were censored at their last known alive date recorded within the PETP. All deaths, regardless of causality or whether they were reported as a reason for study discontinuation, are reported in the All-Cause Mortality section.
measure
All-cause Mortality
time Frame
Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.)
description
CVHs were those events that were adjudicated and confirmed as such by the CEAC. Frequency of CEAC-adjudicated CVH was calculated using negative binomial regression analysis with study intervention, study, geographic region, daratumumab usage at Baseline, and offset term equal to log of each participant's follow-up time for cardiovascular hospitalization included in the model.
measure
Frequency of CVHs
time Frame
Day 1 through end of the participant's PETP (Participants were enrolled on a rolling basis. Therefore, analysis for the study was conducted 18-47 months after the study randomization.)
description
Change in heart function was measured by GLS%, a noninvasive imaging technique that uses echocardiography to assess heart. GLS% expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) and is reported as a negative value. A more negative value is usually associated with cardiac enhancement.
measure
Change From Baseline in Global Longitudinal Strain (GLS%)
time Frame
Baseline, Week 50
description
The SF-36v2 is a self-administered questionnaire containing 36 items that measure health on functional status, well-being, and overall evaluation of health in 8 domains, including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health, using scaled, ordinal responses (for example, All of the time, Most of the time, A good bit of the time). The SF-36v2 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, with higher scores indicating an increased quality of life. The 8 multi-item scales are aggregated and summed to give the final PCS. The final score ranges from 0-100, with higher scores indicating an increased quality of life.
measure
Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS)
time Frame
Baseline, Week 50
description
For each participant, blood samples were assayed for NT-proBNP, comparing the participant's baseline value over time to assess reduced amyloidosis, as measured by a decrease in NT-proBNP. A decrease indicates cardiac enhancement. Results reported as nanograms/milliliter (ng/mL).
measure
Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples
time Frame
Baseline, Week 50

Full study description

brief 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, reduces cardiovascular related hospitalizations and it is safe and well tolerated in patients with stage IIIb AL amyloidosis.
detailed 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 IIIb PCD treatment-naïve AL amyloidosis patients. The primary evaluation treatment period (PETP) part of the study will stop when the last patient is randomized in the PETP plus 18 months. Approximately 124 patients will be enrolled using a 2:1 randomization ratio. Stratification will be based on geographic region across investigator sites. The primary endpoint is a composite endpoint of all-cause mortality and frequency of cardiovascular hospitalizations. Patients in both study intervention groups will be followed from randomization until death from any cause, heart transplant, left wall assist device (LVAD) implantation or until the end of study.

Source references

references

citation
Wechalekar AD, Dispenzieri A, Sanchorawala V, Kastritis E, Bhutani D, Bianchi G, Jimenez-Zepeda VH, Suzuki K, Lentzsch S, Huart A, Carpinteiro A, Swenson ES, Khan Z, Catini J, Kulkarni H, Meltzer B, Lake S, Liedtke M; CARES Investigators. Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials. J Clin Oncol. 2026 Jul 10;44(20):1899-1910. doi: 10.1200/JCO-26-00755. Epub 2026 May 29.
pmid
42212672
type
DERIVED