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



Status:Completed
Conditions:Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:18 - Any
Updated:10/20/2017
Start Date:February 2013
End Date:July 2017

Use our guide to learn which trials are right for you!

A Phase I Dose Escalation Study of Carfilzomib in Patients With Previously-Treated Systemic Light-Chain (AL) Amyloidosis

This is a dose finding study to evaluate the safety and determine the maximum tolerated dose
of carfilzomib in patients with previously treated systemic light-chain amyloidosis.

This is a dose finding study to evaluate the safety and determine the maximum tolerated dose
of carfilzomib in patients with previously treated systemic light-chain amyloidosis. The
study will also explore the efficacy of carfilzomib in both proteasome inhibitor-naive and
proteasome inhibitor-exposed patients including hematologic response, organ response,
progression free survival, and time to next therapy.

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:

- 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

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.
We found this trial at
10
sites
1365 Clifton Rd NE
Atlanta, Georgia 30322
(404) 778-1900
Principal Investigator: Jonathan Kaufman, MD
Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
116th St and Broadway
New York, New York 10027
(212) 854-1754
Principal Investigator: Suzanne Lentzsch, MD
Columbia University In 1897, the university moved from Forty-ninth Street and Madison Avenue, where it...
?
mi
from
New York, NY
Click here to add this to my saved trials
1 Boston Medical Center Place
Boston, Massachusetts 02118
617.638.8000
Principal Investigator: Vaishali Sanchorawala, MD
Boston University Medical Center Boston Medical Center is an extraordinary community of health care providers...
?
mi
from
Boston, MA
Click here to add this to my saved trials
Duarte, California 91010
Principal Investigator: Michael Rosenzweig, MD
Phone: 626-256-4673
?
mi
from
Duarte, CA
Click here to add this to my saved trials
2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Principal Investigator: Cristina Gasparetto, MD
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
?
mi
from
Durham, NC
Click here to add this to my saved trials
92 2nd St
Hackensack, New Jersey 07601
(201) 996-5900
Principal Investigator: David Vesole, MD
John Theurer Cancer Center at the Hackensack University Medical Center The mission of the John...
?
mi
from
Hackensack, NJ
Click here to add this to my saved trials
1275 York Ave
New York, New York 10021
(212) 639-2000
Principal Investigator: Heather J Landau, MD
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
?
mi
from
New York, NY
Click here to add this to my saved trials
3400 Civic Center Blvd
Philadelphia, Pennsylvania 19104
(215) 662-6065
Principal Investigator: Adam Cohen, MD
Abramson Cancer Center of the University of Pennsylvania The Abramson Cancer Center of the University...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Portland, Oregon 97227
Principal Investigator: Emma Scott, MD
?
mi
from
Portland, OR
Click here to add this to my saved trials
Stanford, California 94305
Principal Investigator: Michaela Liedtke, MD
?
mi
from
Stanford, CA
Click here to add this to my saved trials