Trial Search Results

A Study to Evaluate the Effectiveness and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis

The purpose of the study is to determine if CAEL-101 combined withstandard of care plasma cell dyscrasia (PCD) treatment helps peoplewithStage IIIb AL amyloidosis that has affected their hearts to livelonger.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Caelum Biosciences

Collaborator: IQVIA Biotech

Stanford Investigator(s):

Intervention(s):

  • Drug: CAEL-101
  • Other: Placebo
  • Drug: cyclophosphamide, bortezomib, and Dexamethasone (CyBorD) regimen

Phase:

Phase 3

Eligibility


Inclusion Criteria:

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

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

      2. Adult, 18 years and older

      3. AL amyloidosis Mayo stage IIIb based on the 2013 European Modification of the
      2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement
      at the time of Screening

      4. Measurable hematologic disease at Screening as defined by at least one of the
      following:

         1. Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or

         2. Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or

         3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL

      5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid
      deposits by at least one of the following:

         1. Immunohistochemistry or

         2. Mass spectrometry or

         3. Characteristic electron microscopy appearance

      6. Cardiac involvement as defined by:

         1. 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

         2. At least one of the following:

      i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or

      ii. Echocardiogram demonstrating a mean left ventricular wall thickness
      (calculated as [IVSd+LPWd]/2) of > 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

      iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis

      7. Planned first-line treatment for plasma cell disorder is a CyBorD-based regimen
      administered as Standard of Care (SoC)

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

         1. Absolute neutrophil count ≥ 1.0 x 109/L

         2. Platelet count ≥ 75 x 109/L

         3. Hemoglobin ≥ 9 g/dL

         4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless
         due to Gilbert's syndrome.

         5. Aspartate aminotransferase (AST) ≤ 3 x ULN

         6. Alanine aminotransferase (ALT) ≤ 3 x ULN

         7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly
         and isozymes specific to liver, rather than bone)

      9. Women of childbearing potential (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

   10. Men must be surgically sterile or must agree to use effective physician approved
      contraception and refrain from donating sperm from Screening to at least 5 months
      following the last study drug administration or 12 months following the last dose
      of his PCD therapy, whichever is longer.

Exclusion Criteria:

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

      1. Have any other form of amyloidosis other than AL amyloidosis

      2. Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure
      of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL
      amyloidosis and prior to randomization is allowed.

      3. Meets the International Myeloma Working Group (IMWG) definition of multiple
      myeloma or POEMS syndrome

      4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic
      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

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

      6. Taking doxycycline

      7. Receiving dialysis

      8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem
      cell collection during the protocol therapy is permitted.

      9. 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.

   10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening

   11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area
      < 1.0 cm2) or severe congenital heart disease

   12. 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. (Participants who do have a pacemaker or ICD are
      allowed in the study.)

   13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a
      pacemaker may be included regardless of calculated QTc interval.

   14. There is evidence of acute ischemia or active conduction system abnormalities
      with the exception of any of the following:

         1. First degree Atrioventricular (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. (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)

   15. 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

   16. There is 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

         4. Other localized and/or low risk malignancies may be permitted with Medical
         Monitor approval.

   17. Have received an investigational drug/device in another clinical investigational
      study within 60 days before Screening

   18. Hypersensitivity to the study drug

   19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD

   20. Women who are breast feeding

   21. 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.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Mani Gupta
650-723-0501
Recruiting