A Study to Evaluate the Safety and Effectiveness of CAEL-101 and Plasma Cell Dyscrasia Treatment vs. Placebo and Plasma Cell Dyscrasia Tretment to Treat Patients with Mayo Stage IIIb AL Amyloidosis

Overview

About this study

The purpose of this study is to determine if CAEL-101 and treatment for plasma cell dyscrasia improves overall survival in Mayo stage IIIb AL amyloidosis patients who are treatment naïve compared to treatment for plasma cell dyscrasia alone, and to evaluate the safety and tolerability of CAEL-101 in combination with treatment for plasma cell dyscrasia.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Provide written informed consent and be willing and able to comply with all study procedures.
  • Adult, 18 years and older.
  • AL amyloidosis stage IIIb based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement (Wechalekar 2013, Dispenzieri 2004) 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 ratio; or
    • Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL.
  • Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid deposits by at least one of the following:
    • Immunohistochemistry; or  
    • Mass spectrometry; or
    • Characteristic electron microscopy appearance.
  • 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
      • Echocardiogram demonstrating a mean left ventricular wall thickness > 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  
      • Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis.
  • Planned first-line treatment for plasma cell disorder is CyBorD administered as Standard of Care (SoC).
  • Adequate bone marrow reserve and hepatic and renal function as demonstrated by:
    • Absolute neutrophil count ≥ 1.0 x 10^9/L;
    • Platelet count ≥ 75 x 10^9/L;
    • Hemoglobin ≥ 9 g/dL;
    • Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless  due to Gilbert's syndrome;
    • Aspartate aminotransferase (AST) ≤ 3 x ULN;
    • Alanine aminotransferase (ALT) ≤ 3 x ULN;
    • Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly  and isozymes specific to liver, rather than bone).
  • WOCBP must have a negative pregnancy test during Screening and must agree to use highly effective physician approved 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 effective physician approved contraception from Screening to 90 days following the last study drug administration.

Exclusion Criteria:

  • 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 syndrome or multiple myeloma defined as clonal bone marrow plasma cells > 10% or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of the following CRAB features:
    • Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
      • Hypercalcemia: serum calcium > 0.25 mmol/L (> 1mg/dL) higher than the ULN or > 2.75 mmol/L (> 11mg/dL);
      • Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177mol/L (> 2mg/dL);
      • Anemia: hemoglobin value of > 20g/L below the lowest limit of normal, or a hemoglobin value < 100g/L;
      • Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. 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
    • Any one of the following biomarkers of malignancy:
      • 60% or greater clonal plasma cells on bone marrow examination;
      • 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 ortHave had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor.
  • LVEF is < 40% by echocardiogram at Screening per site cardiology interpretation 11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2 ) or severe congenital heart disease.
  • Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Patients who do have a pacemaker or ICD are allowed in the study).
  • QT corrected by Fridericia (QTcF) is > 500 msec on Screening ECG. Patients with a QTcF of > 500 msec who have a QRS of > 120 msec and confirmed right bundle branch block, left bundle branch block or intraventricular conduction defect may be considered for enrollment in consultation with the Medical Monitor. Patients who have a pacemaker may be included regardless of calculated QTc interval.
  • There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
    • First degree atrioventricular block;
    • Second degree atrioventricular block Type 1 (Mobitz Type 1/Wenckebach type)a;
    • Right or left bundle branch blockhostatic 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.
  • Taking prednisone or its equivalent > 10 mg/day.
  • Taking doxycycline.
  • Receiving dialysis.
  • Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted.
  • Have had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor.
  • LVEF is < 40% by echocardiogram at Screening per site cardiology interpretation.
  • Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2 ) or severe congenital heart disease.
  • Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Patients who do have a pacemaker or ICD are allowed in the study.)
  • QT corrected by Fridericia (QTcF) is > 500 msec on Screening ECG. Patients with a QTcF of > 500 msec who have a QRS of > 120 msec and confirmed right bundle branch block, left bundle branch block or intraventricular conduction defect may be considered for enrollment in consultation with the Medical Monitor. Patients who have a pacemaker may be included regardless of calculated QTc interval.
  • There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
    • First degree atrioventricular block;
    • Second degree atrioventricular block Type 1 (Mobitz Type 1/Wenckebach type);
    • Right or left bundle branch block.
    • Atrial fibrillation with a controlled ventricular rate. (An uncontrolled ventricular rate [i.e., > 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed).
  • Have had major surgery within 4 weeks of randomization or is planning major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate.
  • There is active malignancy (including lymphoma) with the exception of any of the following:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer;
    • Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years;
    • Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL;
    • Other localized and/or low risk malignancies may be permitted with Medical Monitor approval.
  • Have received an investigational drug/device in another clinical investigational study within 60 days before Screening.
  • Hypersensitivity to the study drug.
  • Have received a live vaccine within 4 weeks prior to first dose of CyBorD.
  • Women who are breast feeding.
  • Have any other medical, social or psychological factors that could affect the patient’s safety or ability to consent personally or comply with study procedures.

Eligibility last updated 12/7/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Taimur Sher, M.B.B.S., M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Angela Dispenzieri, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeremy Larsen, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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CLS-20513443

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