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)
assay, defined as a dFLC of at least 50 mg/L (5 mg/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
following:

- 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 mL/min]

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

- 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
guidelines

- 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
intercourse

- 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.
Valacyclovir)

- 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
impairment

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