Trial Search Results

A Safety Study of Carfilzomib in Patients With Previously-Treated Systemic Light Chain Amyloidosis

The main purpose of this study is to evaluate the safety and determine the maximum tolerated dose of an investigational new drug, carfilzomib, in people with previously-treated AL amyloidosis. The study will also evaluate how well the participant's disease responds to this treatment.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

Criterium, Inc.

Collaborator: Amgen

Stanford Investigator(s):


  • Drug: Carfilzomib
  • Drug: Dexamethasone


Phase 1


Inclusion Criteria:

   - Males and females ≥ 18 years of age

   - Histologically-proven AL amyloidosis, confirmed by positive Congo red stain with green
   birefringence on polarized light microscopy with evidence of measurable clonal disease
   that requires active treatment as defined below:

   - Patients must have clonal disease measureable by serum free light chain (FreeliteTM)

      - For the dose-escalation cohort: this is defined as having any elevation in the
      amyloidogenic (i.e. clonal) light chain with an abnormal free kappa:lambda ratio

      - For the dose expansion cohorts: in addition to the above, there must be a
      difference between the amyloidogenic (i.e. clonal) and non-amyloidogenic light
      chain (dFLC) of at least 50mg/L (5mg/dL)

   - Relapsed (progressed after prior response) or refractory (failed to achieve at least a
   partial response) to at least one prior therapy for amyloidosis.

      - Patients that received an autologous stem cell transplant must be at least 3
      months post-transplant and recovered from acute transplant-related toxicities.

      - Patients that were unable to tolerate at least 1 cycle of an alkylating agent
      plus corticosteroid (e.g. melphalan + dexamethasone) or alternative prior regimen
      because of severe adverse events (e.g. hypersensitivity reaction) may be
      considered after discussion with the study PI/Medical Monitor.

   - Objective, measureable, symptomatic organ involvement, defined as one or more of the

      - Kidney: albuminuria ≥ 500 mg/day in a 24-hour urine specimen

      - Heart: presence of mean left ventricular wall thickness on echocardiogram greater
      than 12 mm in the absence of hypertension or valvular heart disease, or
      unexplained low voltage (< 0.5 mV) on ECG, or NT-proBNP > 332 ng/L in the absence
      of impaired renal function [estimated glomerular filtration rate (eGFR) < 45

      - Liver: hepatomegaly on physical exam with elevated alkaline phosphatase > 1.5 x

      - GI Tract: biopsy showing amyloid deposition along with symptoms such as GI
      bleeding or persistent diarrhea (> 4 loose stools/day) Autonomic or Peripheral
      Nervous System: defined as orthostasis, symptoms of nausea or dysgeusia,
      recurrent diarrhea or constipation, abnormal sensory and/or motor findings on
      neurologic exam, or gastric atony by gastric emptying scan

      - Note: Skin, lymph node, or soft tissue involvement; carpal tunnel syndrome; or
      bone marrow amyloid as the sole clinical manifestations of amyloidosis are not
      sufficient for inclusion.

   - Amyloid cardiac biomarker stage I or II disease Staging defined by NT-proBNP and
   troponin T cut-offs of < 332 pg/mL and <0.035 ng/mL, respectively, as thresholds:
   Stage I, both under threshold; and Stage II, either troponin or NT-proBNP (but not
   both) over threshold. If troponin T is not available at local institution, troponin I
   may be used, but threshold is <0.1 ng/mL.23

   - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

   - Clinical laboratory values as specified within 14 days of treatment:

      - Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

      - Hemoglobin ≥8 g/dL [transfusion permitted]

      - Platelet count ≥75.0 x 109/L

      - Total bilirubin ≤ 2 x Upper Limit of Normal (ULN)

      - Alkaline phosphatase ≤ 5 x ULN

      - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.5 x ULN

      - CrCl ≥ 30 mL/min as measured by 24-hour urine

      - Screening ANC should be independent of granulocyte-and granulocyte/macrophage
      colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of
      pegylated G-CSF for at least 2 weeks

      - Screening platelet count should be independent of platelet transfusions for at
      least 2 weeks

   - Written informed consent in accordance with federal, local, and institutional

   - Females of childbearing potential must agree to ongoing pregnancy testing and to
   practice contraception or abstain from heterosexual intercourse

   - Male patients must agree to practice contraception or to abstain from heterosexual

   - Male patients must agree not to donate semen or sperm

   - Life expectancy of ≥ 3 months

Exclusion Criteria:

   - Pregnant or lactating females

   - Major surgery within 21 days prior to first dose

   - Acute active infection requiring systemic antibiotics, antivirals, or antifungals
   within 14 days prior to first dose

   - Treatment with an experimental drug within 28 days of first dose

   - Active Human Immunodeficiency Virus (HIV) or hepatitis B or C infection

   - Bone marrow plasma cells ≥ 30% or clinical manifestations of multiple myeloma, such as
   hypercalcemia or lytic bone lesions

   - Cardiac exclusions:

      - Left ventricular ejection fraction (LVEF) < 40%

      - Amyloid cardiac biomarker stage III disease, defined as both NT-proBNP ≥ 332
      pg/mL and troponin T ≥ 0.035 ng/mL. If troponin T is not available at local
      institution, troponin I may be used, but cut-off is ≥ 0.1 ng/mL

      - New York Heart Association (NYHA) classification III or IV heart failure (see
      Appendix G) despite medical management

      - Unstable angina or myocardial infarction within 6 months prior to first dose

      - Grade 2 or 3 atrioventricular (AV) block (Mobitz type I is permitted) or sick
      sinus syndrome, unless subject has a pacemaker

      - Known history of sustained (> 30 second) ventricular tachycardia or cardiac
      syncope. Known history of recurrent non-sustained ventricular tachycardia (> 3
      beats) despite anti-arrhythmic therapy

      - Supine systolic blood pressure < 90 mm Hg, or symptomatic orthostatic
      hypotension, or a decrease in systolic blood pressure upon standing of > 20 mm Hg
      despite medical management (e.g. midodrine, fludrocortisones)

   - Significant peripheral neuropathy (Grade 3, Grade 4, or Grade 2 with pain) within 14
   days prior to first dose

   - Severe diarrhea (≥ grade 3) not controllable with medication or that requires total
   parenteral nutrition

   - History of bleeding diathesis, known factor X deficiency (level < 20%), or requirement
   for therapeutic anticoagulation with warfarin

   - Known allergies to carfilzomib or Captisol® (a cyclodextrin derivative used to
   solubilize carfilzomib)

   - Presence of other active malignancy with the exception of non-melanoma skin cancer,
   cervical cancer, treated early-stage prostate cancer provided that prostate-specific
   antigen is within normal limits, or any completely resected carcinoma in situ

   - Serious psychiatric or medical conditions that could interfere with treatment

   - Contraindication to any of the required concomitant drugs, including antiviral (e.g.

   - Patients in whom the required program of oral and IV fluid hydration is
   contraindicated, e.g. due to severe pre-existing pulmonary, cardiac, or renal

   - Subjects with pleural effusions requiring thoracentesis or ascites requiring
   paracentesis within 14 days prior to first dose.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study


Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office
Not Recruiting