A Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis

NCT04304144 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CAEL101-203
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

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 .

Conditions

AL Amyloidosis

Keywords

cyclophosphamide, bortezomib and dexamethasone (CyBorD); AL Amyloidosis; Amyloid, Light chain Amyloidosis; Mayo Stage IIIa; daratumumab; Mayo Stage II; Mayo Stage I

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  4 weeks

Secondary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of CAEL-101

  Predose through Week 1 and through Week 20

• Area Under Plasma Concentration-time Curve Over Dosing Interval (AUCtau) of CAEL-101

  Predose through Week 1 and through Week 20

Study Arms (2)

Part A: CAEL-101 combined with SoC CyBorD

EXPERIMENTAL

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)

Part B: CAEL-101 combined with SoC CyBorD and daratumumab

EXPERIMENTAL

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

Interventions

CAEL-101 DRUG

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

Part A: CAEL-101 combined with SoC CyBorD; Part B: CAEL-101 combined with SoC CyBorD and daratumumab

SoC: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) DRUG

According to institutional standard of care.

Part A: CAEL-101 combined with SoC CyBorD; Part B: CAEL-101 combined with SoC CyBorD and daratumumab

Daratumumab DRUG

Treatment for AL amyloidosis

Part B: CAEL-101 combined with SoC CyBorD and daratumumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Each patient must meet the following criteria to be enrolled in this study.
• AL amyloidosis Mayo stage I, II or IIIa
• For Part A only, measurable hematologic disease defined by at least one of the following:
• involved/uninvolved free light chain difference (dFLC) \> 5mg/dL or
• free light chain (FLC) \> 5mg/dL with abnormal Kappa/Lambda ratio or
• serum protein electrophoresis (SPEP) m- spike \> 0.5 g/dL Patients with confirmed AL amyloid diagnosis without measurable disease may be enrolled with consultation and approval by the Sponsor Medical Monitor or their designee.
• a. For Part A, currently on and continuing OR planned to start concurrent chemotherapy with CyBorD administered weekly as SoC. b. For Part B, currently on and continuing OR planned to start concurrent chemotherapy with CyBorD and daratumumab administered as SoC.

You may not qualify if:

• Patients who meet any of the following criteria will not be permitted entry to the study.
• Any form of secondary, hereditary, senile, localized, dialysis-related or leukocyte chemotactic factor 2-related (ALECT2) amyloidosis
• Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma. Patients with signs and/or symptoms attributable ONLY to amyloidosis and who do NOT meet IMWG definition of smoldering myeloma may be enrolled upon approval of the medical monitor.
• Supine systolic blood pressure \< 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of \> 20 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
• Receiving dialysis
• Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or percutaneous cardiac intervention with recent stent, coronary artery bypass grafting or major cerebrovascular accident within 6 months prior to screening
• Left ventricular ejection fraction (LVEF) \< 45 percent by echocardiogram or multigated acquisition scan (MUGA)

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (3)

Research Site

Stanford, California, 94305, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Bortezomib; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multicenter, open-label, sequential cohort, dose-selection study of CAEL-101 in Mayo Stage I, II and IIIa AL amyloidosis patients. The study is divided into two parts: * Part A defines the safety and tolerability of CAEL-101 in combination with SoC CyBorD and determines the RP3D * Part B evaluates the safety and tolerability of CAEL-101 in combination with SoC CyBorD and daratumumab Part A 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. Part B will enroll a minimum of 6 patients. Patients will be seen in the clinic weekly for 4 weeks to receive study drug infusions. Study drug infusions will be bi-weekly thereafter or every 4 weeks after 50 weeks, if participants switch to an alternative dosing schedule. Patients are treated until death, toxicity, symptomatic deterioration, Investigator, patient, or Sponsor decision to terminate.

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 11, 2020
• Study Start: March 18, 2020
• Primary Completion: November 14, 2023
• Study Completion: November 14, 2023
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (3)