A Phase I Dose Escalation Study of Carfilzomib in Patients With Previously-Treated Systemic Light-Chain (AL) 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 not currently accepting new patients for this trial. You may want to check clinicaltrials.gov to see if other locations are recruiting.
- drug : Dexamethasone
- drug : Carfilzomib
Phase: Phase 1
Ages Eligible For Study:
- 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: - 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 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