AL AmyloidosisPhase 3NCT04504825
A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (CARES)
A Phase 3 study testing CAEL-101 and cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen in people with AL Amyloidosis, run by Alexion Pharmaceuticals, Inc. at 90 sites in 19 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- CAEL-101 and cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 90 sitesin 19 countries
- Study dates
- 25 Aug 2020to 22 Oct 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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:
Show all 16Show fewer
- Immunohistochemistry/Immunofluorescence or
- Mass spectrometry or
- Characteristic electron microscopy appearance/Immunoelectron microscopy
- 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:
- 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
Who cannot join
- 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:
- 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
Trial locations and contacts
90 sites in 19 countries.
90 sites in 19 countries
United States26 sites
Research Site
Boston, Massachusetts, 02111
Research Site
Boston, Massachusetts, 02118
Research Site
Boston, Massachusetts, 02215
Research Site
Cleveland, Ohio, 44195
Research Site
Columbus, Ohio, 43210
Research Site
Dallas, Texas, 75390
Research Site
Detroit, Michigan, 48201
Research Site
Duarte, California, 91010
Research Site
Houston, Texas, 77030
Research Site
Indianapolis, Indiana, 46202
Research Site
Milwaukee, Wisconsin, 53226
Research Site
Nashville, Tennessee, 37232
Research Site
New Orleans, Louisiana, 70112
Research Site
New York, New York, 10032
Research Site
New York, New York, 10065
Research Site
Palo Alto, California, 94304
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon, 97239
Research Site
Rochester, Minnesota, 55905
Research Site
Rochester, New York, 14642
Research Site
Salt Lake City, Utah, 84112
Research Site
San Francisco, California, 94143
Research Site
Seattle, Washington, 98109
Research Site
St Louis, Missouri, 63110
Research Site
Weston, Florida, 33331
Research Site
Winston-Salem, North Carolina, 27157
France11 sites
Research Site
Caen, 14033
Research Site
Créteil, 94000
Research Site
Limoges, 87042
Research Site
Marseille, 13009
Research Site
Paris, 75010
Research Site
Pessac, 33604
Research Site
Pierre-Bénite, 69310
Research Site
Poitiers, 86021
Research Site
Rennes, 35033
Research Site
Toulouse, 31100
Research Site
Tours, 37044
Germany6 sites
Research Site
Berlin, 13353
Research Site
Düsseldorf, 40225
Research Site
Essen, 45147
Research Site
Hamburg, 22767
Research Site
Heidelberg, 69120
Research Site
Würzburg, 97080
Spain6 sites
Research Site
Barcelona, 08036
Research Site
Barcelona, 8035
Research Site
Gijón, 33394
Research Site
Majadahonda, 28222
Research Site
Pamplona, 31008
Research Site
Seville, 41013
China5 sites
Research Site
Beijing, 100730
Research Site
Guangzhou, 510180
Research Site
Hangzhou, 310009
Research Site
Wenzhou, 325000
Research Site
Wuhan, 430022
Brazil4 sites
Research Site
Porto Alegre, 90110-270
Research Site
Ribeirão Preto, 14048-900
Research Site
Salvador, 41253-190
Research Site
São José do Rio Preto, 15090-000
Italy4 sites
Research Site
Naples, 80131
Research Site
Pavia, 27100
Research Site
Pisa, 56126
Research Site
Roma, 00128
Australia3 sites
Research Site
Box Hill, 3128
Research Site
Brisbane, 4102
Research Site
Westmead, 2145
Canada3 sites
Research Site
Calgary, Alberta, T2N 4N2
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Toronto, Ontario, M5G 2M9
Israel3 sites
Research Site
Haifa, 31096
Research Site
Jerusalem, 91120
Research Site
Tel HaShomer, 52621
Japan3 sites
Research Site
Fukushima, 960-1295
Research Site
Nagoya, 467-8602
Research Site
Shibuya-ku, 150-8935
Poland3 sites
Research Site
Gdansk, 80-214
Research Site
Poznan, 60-569
Research Site
Warsaw, 01-748
Czechia2 sites
Research Site
Ostrava - Poruba, 70852
Research Site
Prague, 12808
Netherlands2 sites
Research Site
Groningen, 9713 GZ
Research Site
Utrecht, 3508 GA
About this study
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
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.
Read the 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.
- Conditions
- AL Amyloidosis
- Being tested
- CAEL-101, Placebo, cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen
- Keywords
- Plasma Cell Dyscrasia, cyclophosphamide, bortezomib and dexamethasone (CyBorD), AL Amyloidosis, Amyloid, Light chain Amyloidosis, treatment-naïve, Mayo Stage IIIb
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Paraproteinemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAEL-101Drug
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.
PlaceboOther
Commercially available 0.9% Normal Saline will be used as the placebo.
cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimenDrug
According to institutional standard of care.
| Study group | Role | What they receive |
|---|---|---|
| CAEL-101 combined with SoC plasma cell dyscrasia | Experimental | 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. Receives: Drug: CAEL-101; Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen |
| Placebo combined with SoC plasma cell dyscrasia | Placebo comparator | 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. Receives: Other: Placebo; Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
A Hierarchical Combination of Time to All-cause Mortality and Frequency of Cardiovascular Hospitalizations (CVHs) Analyzed by Win Ratio
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.
Measured: 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.)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Measured: 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 (7)
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
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).
Measured: Baseline, Week 50
Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT)
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.
Measured: Baseline, Week 50
All-cause Mortality
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.
Measured: 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.)
Frequency of CVHs
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.
Measured: 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.)
Change From Baseline in Global Longitudinal Strain (GLS%)
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.
Measured: Baseline, Week 50
Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS)
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.
Measured: Baseline, Week 50
Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples
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).
Measured: Baseline, Week 50
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2020
- Study start25 Aug 2020
- Primary completion10 May 2025
- Study completion22 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Swenson, MD, Study director, Alexion, AstraZeneca Rare Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04504825
- Sponsor's protocol ID
- CAEL101-301
- Status last verified
- Jun 2026
- First submitted
- 20 Jul 2020
- Last updated
- 2 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Patient numbers will not be reassigned. Any patient records or datasets transferred to the Sponsor must contain only the unique identifier and must not include patient names or any information which would make the patient identifiable. Patients will be informed that their personal study-related data will be used by the Sponsor in accordance with local data protection laws and that their medical records may be examined by representatives of the Sponsor, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) members and by inspectors from regulatory authorities. Study monitors will inspect all documents and records that are required to be maintained by the Investigator for this study.
Publications
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.
PubMed 42212672
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04504825
- Acronym / sponsor ID
- CAEL101-301
- Conditions
- AL Amyloidosis
- Keywords
- Plasma Cell Dyscrasia, cyclophosphamide, bortezomib and dexamethasone (CyBorD), AL Amyloidosis, Amyloid, Light chain Amyloidosis, treatment-naïve, Mayo Stage IIIb
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 10 May 2025 (actual)
- Study completion
- 22 Oct 2027 (estimated)
- First posted
- 7 Aug 2020 (actual)
- Results
- Posted 2 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| CAEL-101 combined with SoC plasma cell dyscrasia | Experimental | Drug: CAEL-101, Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimenCAEL-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. |
| Placebo combined with SoC plasma cell dyscrasia | Placebo comparator | Other: Placebo, Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimenPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- 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:
- Cardiac involvement as defined by:
- Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC
Key exclusion criteria (5 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAEL-101The 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. | Drug | CAEL-101 combined with SoC plasma cell dyscrasia |
| PlaceboCommercially available 0.9% Normal Saline will be used as the placebo. | Other | Placebo combined with SoC plasma cell dyscrasia |
| cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimenAccording to institutional standard of care. | Drug | CAEL-101 combined with SoC plasma cell dyscrasia, Placebo combined with SoC plasma cell dyscrasia |
Primary outcome
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.)
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.
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.)
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.
7 secondary outcomes
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)
Time frame: Baseline, Week 50
Change From Baseline in Distance Walked During a Six-minute Walk Test (6MWT)
Time frame: Baseline, Week 50
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.)
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.)
Change From Baseline in Global Longitudinal Strain (GLS%)
Time frame: Baseline, Week 50
Change From Baseline in the Short Form-36 (SF-36) Version 2 (v2) Physical Component Score (PCS)
Time frame: Baseline, Week 50
Change From Baseline in N-Terminal Pro-B-type Natriuretic Peptide (NT-proBNP) in Blood Samples
Time frame: Baseline, Week 50
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42212672Wechalekar 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.
- CSR Synopsis - RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Patient numbers will not be reassigned. Any patient records or datasets transferred to the Sponsor must contain only the unique identifier and must not include patient names or any information which would make the patient identifiable. Patients will be informed that their personal study-related data will be used by the Sponsor in accordance with local data protection laws and that their medical records may be examined by representatives of the Sponsor, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) members and by inspectors from regulatory authorities. Study monitors will inspect all documents and records that are required to be maintained by the Investigator for this study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Swenson, MD study director
Alexion, AstraZeneca Rare Disease
90 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CAEL-101 and cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen in people with AL Amyloidosis, run by Alexion Pharmaceuticals, Inc. at 90 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in United States, France, Germany, Spain, China and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04504825, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.