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

• Status: Active, not recruiting
• Trial end date: 2023-01-23
• Target enrollment: 0
• Participant gender: All

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 .

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Caelum Biosciences
• Treatments: Bortezomib; Cyclophosphamide; Daratumumab; Dexamethasone

Criteria

Inclusion Criteria:

Each patient must meet the following criteria to be enrolled in this study.

1. Provide written informed consent and be willing and able to comply with all study procedures

2. Adult, 18 years and older

3. Minimum life expectancy of 6 months

4. AL amyloidosis Mayo stage I, II, or IIIa at the time of Screening

5. Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance

6. 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.

7. Adequate bone marrow reserve and hepatic function as demonstrated by:

8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during Screening and must agree to use effective physician-approved contraception from Screening to 90 days following the last study drug administration

9. Men must be surgically sterile or must agree to use effective physician-approved contraception from Screening to 90 days following the last study drug administration

Exclusion Criteria:

Patients who meet any of the following criteria will not be permitted entry to the study.

1. Any form of secondary, hereditary, senile, localized, dialysis-related or leukocyte chemotactic factor 2-related (ALECT2) amyloidosis

2. Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma.

3. 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

4. Taking prednisone or its equivalent > 10 mg/day

5. Receiving dialysis

6. Planned stem cell transplant during the first 6 months of protocol therapy.

7. 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

8. Left ventricular ejection fraction (LVEF) < 45 percent by echocardiogram or multigated acquisition scan (MUGA) within the last 6 months

9. Severe valvular stenosis (e.g. aortic or mitral stenosis with a valve area <1.0 cm^2) or severe congenital heart disease

10. History of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillators (ICD) is indicated but not placed (participants who do have a pacemaker/ICD are allowed on study)

11. QTcF > 500 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval.

12. Evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:

1. First degree AV-block

2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)

3. Right or left bundle branch block

4. Atrial fibrillation with a controlled ventricular rate (uncontrolled [i.e., >110 bpm] ventricular rate is not allowed [determined by an average of three beats in Lead II or representative beats if Lead II is not representative of the overall ECG])

13. Major surgery within 4 weeks of first dose or planned major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate.

14. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes)

15. Active malignancy (including lymphoma) with the exception of any of the following:

1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer

2. Adequately treated Stage I cancer from which the patient is currently in remission and has been in remission for > 2 years

3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL

16. Patients receiving an investigational drug/device in another clinical investigational study within 60 days before Screening

17. Nursing mothers will not be permitted entry into the study.