- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04304144
A Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis
CAEL101-203: A Phase 2, Open-label, Multicenter Dose Selection Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis
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 .
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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:
- Part A defines the safety and tolerability of CAEL-101 in combination with SoC CyBorD and determines the recommended Phase 3 dose (RP3D) of CAEL-101
- Part B evaluates the safety and tolerability of CAEL-101 in combination with SoC CyBorD and daratumumab
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Palo Alto, California, United States, 94305
- Clinical Trial Site
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Michigan
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Detroit, Michigan, United States, 48201
- Clinical Trial Site
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Ohio
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Cleveland, Ohio, United States, 44195
- Clinical Trial Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
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.
Key Exclusion Criteria:
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part A: CAEL-101 combined with SoC CyBorD
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).
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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.
Other Names:
According to institutional standard of care.
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Experimental: Part B: CAEL-101 combined with SoC CyBorD and daratumumab
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.
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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.
Other Names:
According to institutional standard of care.
Treatment for AL amyloidosis
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicity
Time Frame: 4 weeks
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Occurrence of dose limiting toxicity (DLT) during the first 4 weeks of therapy (Part A)
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4 weeks
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Safety Parameters
Time Frame: Through the study completion, an average of 4 years
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Treatment-emergent serious adverse events (SAEs) and adverse events (AEs), AEs leading to treatment discontinuation, abnormal laboratory tests of clinical relevance, abnormal physical examination, abnormal vital signs, abnormal electrocardiogram (ECG) parameters of clinical relevance
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Through the study completion, an average of 4 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety parameters to be assessed separately for Parts A (CAEL 101 when administered in combination with standard-of-care CyBorD) and B (CAEL 101 when administered in combination with standard-of-care CyBorD and daratumumab)
Time Frame: Through the study completion, an average of 4 years
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Treatment-emergent SAEs and AEs, AEs leading to treatment discontinuation, abnormal physical examination findings, abnormal vital signs, abnormal ECG parameters of clinical relevance, and changes in clinical safety laboratory parameters of potential clinical concern
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Through the study completion, an average of 4 years
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PK Parameters (bi-weekly versus monthly CAEL-101 dosing))
Time Frame: Through the study completion, an average of 4 years
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Maximum concentration, minimum concentration, and area under the concentration-time curve
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Through the study completion, an average of 4 years
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Paraproteinemias
- Proteostasis Deficiencies
- Neoplasms, Plasma Cell
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dexamethasone
- Cyclophosphamide
- Daratumumab
- Bortezomib
Other Study ID Numbers
- CAEL101-203
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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