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AmyloidosisPhase 1NCT01789242

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

A Phase 1 study testing Carfilzomib and Dexamethasone in people with Amyloidosis and Systemic Light Chain Amyloidosis, run by Criterium, Inc. at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyloidosis, Systemic Light Chain Amyloidosis
What is being tested?
Carfilzomib and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
10 sitesUnited States
Study dates
Feb 2013to Jul 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • City of Hope

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Columbia University

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Abramson Cancer Center at the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Sciences University

    Portland, Oregon, 97239

  • Stanford Cancer Institute

    Stanford, California, 94305

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Medical subject headings
Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called PR-171, Kyprolis

    IV over 30 minutes on Days 1, 2, 8, 9, 15, and 16 every 28 days.

  • DexamethasoneDrug

    Also called Decadron

    Dexamethasone IV or PO on Days 1, 2, 8, 9, 15, and 16 every 28 days in patients with <VGPR after 4 cycles.

Study groups in NCT01789242
Study groupRoleWhat they receive
CarfilzomibExperimentalAll eligible subjects will receive the study intervention of Carfilzomib. Patients with suboptimal hematologic responses (<VGPR after 4 cycles) will have Dexamethasone added to their treatment.
Receives: Drug: Carfilzomib; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Events as a Measure of Safety and Tolerability

    Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment

    Measured: Throughout treatment, estimated at 8 months per patient

Secondary outcomes (4)

  1. Hematologic Response

    Hematologic Response Rates (PR, VGPR, and CR

    Measured: Every 28 days while on treatment (estimated at 8 months per patient)

  2. Organ Response

    Organ response rates by standard criteria

    Measured: Every 112 days while on treatment (estimated at 8 months per patient)

  3. Progression Free Survival

    Measured: throughout study and follow up (every 2-3 months for 2 years

  4. Time to next therapy

    Measured: throughout follow up (every 2-3 months for 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2013 (estimated)
  2. Study startFeb 2013
  3. Primary completionDec 2016
  4. Study completionJul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01789242
Sponsor's protocol ID
AMyC 11MM02
Other IDs
IST-CAR-545
Status last verified
Oct 2017
First submitted
6 Feb 2013
Last updated
18 Oct 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib and Dexamethasone in people with Amyloidosis and Systemic Light Chain Amyloidosis, run by Criterium, Inc. at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events as a Measure of Safety and Tolerability (time frame: Throughout treatment, estimated at 8 months per patient). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01789242.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2017.

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