A Phase 2 interventional study of CAEL-101 and SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) in AL Amyloidosis, sponsored by Alexion Pharmaceuticals, Inc.. Completed at 3 sites in United States. Per ClinicalTrials.gov, last updated 2025-03-05.
Sponsored by Alexion Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
AL 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 the recommended dose of CAEL-101 to facilitate progression of further clinical trials and evaluate safety and tolerability of CAEL-101 in combination with the standard of care (SoC) cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy and daratumumab .
This is a multicenter, open-label, sequential cohort, dose-selection study of CAEL-101 in Mayo Stage I, Stage II and Stage IIIa AL amyloidosis patients. CAEL-101 will be administered in combination with the standard of care (SoC) cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy and daratumumab.
The study is divided into two parts with the following objectives:
The study will also evaluate the pharmacokinetic profile of CAEL-101 and explore the PK profile of CAEL-101 when given bi-weekly (q2wk) versus once-monthly (q4wk) after the first 50 weeks.
Part A of the study will employ a 3+3 dose escalation design. At least 3 patients will be enrolled in each dose cohort unless adverse events (AE) preventing further dosing are observed. CAEL-101 will be administered in combination with the SoC CyBorD chemotherapy.
In Part B, a minimum of 6 new patients will receive CAEL-101 administered in combination with SoC CyBorD and daratumumab.
Patients from both Parts A and B will receive CAEL-101 therapy weekly and SoC throughout the safety observation period. CAEL-101 study drug infusions will continue, with dosing approximately every two weeks (q2wk) thereafter. SoC will continue per the Investigator's discretion. After completing approximately 50 weeks of treatment, participants may switch to an alternative maintenance dosing regimen of every four weeks (q4wk), if agreed upon by the Investigator and the Sponsor Medical Monitor.
Approximately 25 patients will be enrolled in the study at approximately 3 investigator sites.
Patients will be treated with CAEL-101 until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study.
167 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 57 are open to participants now.
This study's enrollment of 25 is below the median of 37 across 120 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.
Browse Immunoglobulin Light-chain Amyloidosis studies →Alexion Pharmaceuticals, Inc. is the lead sponsor of 249 studies on the registry; 25 are open to participants now.
Of its 98 completed or terminated interventional studies of FDA-regulated products, 70 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Each patient must meet the following criteria to be enrolled in this study.
For Part A only, measurable hematologic disease defined by at least one of the following:
Key Exclusion Criteria:
Patients who meet any of the following criteria will not be permitted entry to the study.
CAEL-101 is administered as an intravenous (IV) infusion over approximately 2 hours. The initial cohort dose assignments of CAEL-101 will be: Cohort 1 - 500 mg/m\^2 Cohort 2 - 750 mg/m\^2 Cohort 3 - 1000 mg/m\^2. CAEL-101 will be administered weekly for the first 4 weeks, and then every other week until end of study, in combination with the SoC CyBorD chemotherapy. Patients will be treated until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study. Patients from Part A who are in the Continued Treatment Period and who, in the Investigator's judgment, should have their SoC treatment complemented with daratumumab may do so (Part B).
Drug: CAEL-101 · Drug: SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD)
CAEL-101 is administered as an intravenous (IV) infusion at the RP3D dose level. CAEL-101 will be administered weekly for the first 4 weeks, and then every other week until end of study, in combination with the SoC CyBorD chemotherapy and daratumumab. After completing approximately 50 weeks of treatment, participants may switch to an alternative maintenance dosing regimen of every four weeks (q4wk), if agreed upon by the Investigator and the Sponsor Medical Monitor. Patients will be treated until death, unacceptable toxicity, symptomatic deterioration, Investigator decision, patient decision or Sponsor decision to terminate the study.
Drug: CAEL-101 · Drug: SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) · Drug: Daratumumab
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.
Also known as: Anselamimab
According to institutional standard of care.
Treatment for AL amyloidosis
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), and AEs Leading to Treatment Discontinuation
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as an AE that started after the first dose of treatment and before the last dose of study drug +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.
Time frame: First dose of study drug until 140 days after last dose of study drug (Maximum exposure: 38.90 months for Part A and 32.50 months for Part B)
Number of Participants With Dose-limiting Toxicity (DLT) During the First 4 Weeks of Therapy
A DLT was defined as any Grade 3 or greater study intervention-related AE that was clinically significant.
Time frame: 4 weeks
Maximum Observed Plasma Concentration (Cmax) of CAEL-101
Time frame: Predose through Week 1 and through Week 20
Area Under Plasma Concentration-time Curve Over Dosing Interval (AUCtau) of CAEL-101
Time frame: Predose through Week 1 and through Week 20
| Milestone | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|
| Started | 4 | 3 | 6 | 0 |
| Received at least 1 dose of study drug | 4 | 3 | 6 | 0 |
| Completed | 4 | 2 | 6 | 0 |
| Not completed | 0 | 1 | 0 | 0 |
| Withdrew: Physician decision | 0 | 1 | 0 | 0 |
| Milestone | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|
| Started | 4 | 2 | 6 | 12 |
| Completed | 1 | 1 | 4 | 6 |
| Not completed | 3 | 1 | 2 | 6 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 1 | 2 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 3 |
| Withdrew: Other than specified | 2 | 0 | 1 | 1 |
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), or an important medical event or reaction. A TEAE was defined as an AE that started after the first dose of treatment and before the last dose of study drug +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.
| Participants | DLT Period (Part A): CAEL-101 500 mg/m^2 | DLT Period (Part A): CAEL-101 750 mg/m^2 | DLT Period (Part A): CAEL-101 1000 mg/m^2 | Overall (Part A): DLT + Continued Treatment Period: CAEL-101 Combined With SoC CyBorD | Continued Treatment Period (Part B): CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|---|
| Any TEAEs | 4 | 3 | 6 | 13 | 12 |
| Treatment-emergent SAEs | 0 | 0 | 2 | 9 | 7 |
| AEs Leading to Treatment Discontinuation | 0 | 0 | 0 | 3 | 1 |
A DLT was defined as any Grade 3 or greater study intervention-related AE that was clinically significant.
| Participants | Part A: CAEL-101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL-101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL-101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) During the First 4 Weeks of Therapy | 0 | 0 | 0 | 0 |
| micrograms (µg)/milliliter (mL) | Part A: CAEL-101 500 mg/m^2 | Part A: CAEL-101 750 mg/m^2 | Part A: CAEL-101 1000 mg/m^2 | Part B: CAEL-101 1000 mg/m^2 |
|---|---|---|---|---|
| Week 1 | 126 ± 16.7 | 255 ± 136 | 244 ± 92.8 | 280 ± 63.0 |
| Week 20 | — | — | 580 ± 270 | 552 ± 194 |
| hours*µg/mL | Part A: CAEL-101 500 mg/m^2 | Part A: CAEL-101 750 mg/m^2 | Part A: CAEL-101 1000 mg/m^2 | Part B: CAEL-101 1000 mg/m^2 |
|---|---|---|---|---|
| Week 1 | 14400 ± 1290 | 27600 ± 12800 | 28600 ± 12700 | 29400 ± 6640 |
| Week 20 | — | — | 147000 ± 69600 | 139000 ± 66700 |
Collected over First dose of study drug until 140 days after last dose of study drug (Maximum exposure: 38.90 months for Part A and 32.50 months for Part B). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DLT Period (Part A): CAEL-101 500 mg/m^2 | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| DLT Period (Part A): CAEL-101 750 mg/m^2 | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| DLT Period (Part A): CAEL-101 1000 mg/m^2 | 0/6 (0%) | 1/6 (16.7%) | 6/6 (100%) |
| Overall (Part A): DLT + Continued Treatment Period: CAEL-101 Combined With SoC CyBorD | 1/13 (7.7%) | 9/13 (69.2%) | 13/13 (100%) |
| Continued Treatment Period (Part B): CAEL-101 Combined With SoC CyBorD and Daratumumab | 2/12 (16.7%) | 7/12 (58.3%) | 11/12 (91.7%) |
| Event | DLT Period (Part A): CAEL-101 500 mg/m^2 | DLT Period (Part A): CAEL-101 750 mg/m^2 | DLT Period (Part A): CAEL-101 1000 mg/m^2 | Overall (Part A): DLT + Continued Treatment Period: CAEL-101 Combined With SoC CyBorD | Continued Treatment Period (Part B): CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|---|
| Cardiac FailureCardiac disorders | 0/4 | 0/3 | 0/6 | 3/13 | 1/12 |
| Clostridium Difficile ColitisGastrointestinal disorders | 0/4 | 0/3 | 1/6 | 0/13 | 0/12 |
| Cardiac Failure AcuteCardiac disorders | 0/4 | 0/3 | 0/6 | 2/13 | 0/12 |
| Splenic InfarctionBlood and lymphatic system disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| Atrial FibrillationCardiac disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| BradycardiaCardiac disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| PalpitationsCardiac disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| Ventricular FibrillationCardiac disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| Non-cardiac Chest PainGeneral disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| Cholecystitis AcuteHepatobiliary disorders | 0/4 | 0/3 | 0/6 | 0/13 | 1/12 |
| Event | DLT Period (Part A): CAEL-101 500 mg/m^2 | DLT Period (Part A): CAEL-101 750 mg/m^2 | DLT Period (Part A): CAEL-101 1000 mg/m^2 | Overall (Part A): DLT + Continued Treatment Period: CAEL-101 Combined With SoC CyBorD | Continued Treatment Period (Part B): CAEL-101 Combined With SoC CyBorD and Daratumumab |
|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 0/4 | 1/3 | 2/6 | 8/13 | 3/12 |
| FatigueGeneral disorders | 1/4 | 0/3 | 1/6 | 8/13 | 5/12 |
| AnaemiaBlood and lymphatic system disorders | 0/4 | 0/3 | 2/6 | 7/13 | 4/12 |
| ConstipationGastrointestinal disorders | 0/4 | 0/3 | 2/6 | 7/13 | 4/12 |
| NauseaGastrointestinal disorders | 2/4 | 1/3 | 1/6 | 7/13 | 4/12 |
| Blood Creatinine IncreasedInvestigations | 1/4 | 0/3 | 1/6 | 7/13 | 1/12 |
| CoughRespiratory, thoracic and mediastinal disorders | 0/4 | 1/3 | 0/6 | 7/13 | 5/12 |
| InsomniaPsychiatric disorders | 2/4 | 0/3 | 1/6 | 5/13 | 2/12 |
| Neuropathy PeripheralNervous system disorders | 0/4 | 0/3 | 0/6 | 6/13 | 3/12 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/4 | 0/3 | 1/6 | 6/13 | 2/12 |
Safety Set included all participants who were treated with at least 1 dose of CAEL-101.
| Age, Categorical(Participants) | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 1 | 1 | 8 | 14 |
| >=65 years | 0 | 2 | 5 | 4 | 11 |
| Sex: Female, Male(Participants) | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab | Total |
|---|---|---|---|---|---|
| Female | 0 | 1 | 2 | 4 | 7 |
| Male | 4 | 2 | 4 | 8 | 18 |
| Ethnicity (NIH/OMB)(Participants) | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 4 | 3 | 6 | 12 | 25 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part A: CAEL101 500 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 750 mg/m^2 Combined With SoC CyBorD | Part A: CAEL101 1000 mg/m^2 Combined With SoC CyBorD | Part B: CAEL-101 Combined With SoC CyBorD and Daratumumab | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 0 | 0 | 2 |
| White | 3 | 2 | 6 | 12 | 23 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
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Immunoglobulin Light-chain Amyloidosis→
Alexion Pharmaceuticals, Inc.