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Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Light Chain Amyloidosis Using PET/CT

Primary Purpose

Cardiac Amyloidosis

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

FNOS

Florbetaben

About this trial

This is an interventional other trial for Cardiac Amyloidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants will be at least 18 years of age
Have an established diagnosis of AL amyloidosis based on standard criteria and planning to start systemic therapy.
Have cardiac involvement as defined by all of the following:
- Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure
- Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness at diastole >12mm in the absence of other causes (e.g. severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
- NT-proBNP ≥ 650 pg/mL
Participants should fall into 1 of the following 2 categories:
1. Treatment-naïve or have completed no more than 1 cycle of initial therapy, OR
2. Relapsed after 1 or more prior therapies, and at least 6 months from last treatment
Have serum free light chain (FLC) differential (defined as amyloid-forming FLC minus non-amyloid-forming FLC) ≥ 50 mg/L.
Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

Females who are pregnant or breast feeding at the time of the PET/CT scan will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential before the injection of radiotracer.
Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
Less than 6 months life expectancy as deemed by a treating physician

Sites / Locations

University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Inflammation group

Amyloid group

Arm Description

Patient diagnosed with Cardiac Amyloidosis

Outcomes

Primary Outcome Measures

Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT

Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy and describe the distributions of uptake values at each time point. Compute post-/pre-treatment fold change in [18F]NOS and Florbetaben uptake and describe its distribution.

Secondary Outcome Measures

Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.

Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Full Information

NCT ID

NCT04105634

First Posted

September 18, 2019

Last Updated

October 2, 2023

Sponsor

University of Pennsylvania

1. Study Identification

Unique Protocol Identification Number

NCT04105634

Brief Title

Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Light Chain Amyloidosis Using PET/CT

Official Title

Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Cardiac Amyloidosis Using Positron Emission Tomography (PET/CT)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 1, 2019 (Actual)

Primary Completion Date

October 1, 2025 (Anticipated)

Study Completion Date

October 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The research study is being conducted to test how two different types of Positron Emission Tomography (PET/CT) scans could be used to image a type of heart disorder called amyloidosis (AL). There will be two groups in the study. One group will have PET/CT scans using an imaging drug called 18F-NOS and the other group will have PET/CT scans using a drug called Florbetaben. subject will be assigned to one of the groups when she/he agrees to be in the study.

Detailed Description

Immunoglobulin light chain (LC) amyloidosis (AL) is an underdiagnosed monoclonal plasma cell proliferative disorder caused by extracellular deposition of AL fibrils in various tissues and organs, causing disease by progressively damaging the structure and function of the affected tissue/organ. The heart is the most commonly involved organ (~75%),9 and the extent and severity of cardiac involvement continue to be the main limitation for successful treatment. Although it remains high, the 6-month mortality rate has improved significantly over the last decade (24% vs. 37%; P<0.001) due to earlier diagnosis, better treatment options, and the advent of sensitive serologic biomarkers to assess for early treatment response,10 in particular serum free light chains (FLC), which permit the differentiation of patients who achieve complete response (CR) and very good partial response (VGPR) from those with partial or no response. N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) has also become a key biomarker for detection and risk-stratification of patients with cardiac AL amyloidosis, and is now routinely employed in clinical trials as a surrogate end point for survival. A large retrospective landmark analysis established that achievement of a CR or VGPR at 6 months post-initiation of therapy, or achievement of an NTproBNP response 6 months post-initiation of therapy, defined as a 30% reduction and absolute reduction ≥ 300 pg/mL from baseline for subjects with baseline levels ≥ 650 pg/mL, was strongly associated with improved overall survival (insert Palladini et al, JCO 2012).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiac Amyloidosis

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Inflammation group

Arm Type

Experimental

Arm Description

Patient diagnosed with Cardiac Amyloidosis

Arm Title

Amyloid group

Arm Type

Experimental

Arm Description

Patient diagnosed with Cardiac Amyloidosis

Intervention Type

Drug

Intervention Name(s)

FNOS

Other Intervention Name(s)

[18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amine

Intervention Description

The imaging drug used for this group is called 18F-NOS, it is an experimental imaging drug that has not yet been approved by the Food and Drug Administration (FDA) for use except in a research study. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.

Intervention Type

Drug

Intervention Name(s)

Florbetaben

Other Intervention Name(s)

Neuraceq

Intervention Description

The imaging drug used for this group is called Florbetaben, it is an FDA approved radioactive PET tracer used to image amyloid plaques in the body. Although not yet FDA approved for this purpose, it has already been used clinically to image amyloid in other parts of the body. Subject will not receive the results or feedback from the study participation, the images may be reviewed with subject or her/his doctor upon request but will not be used to make decisions about subject medical care.

Primary Outcome Measure Information:

Title

Measure uptake of [18F]NOS and Florbetaben in patients with AL before and ~4 months (2 +/- weeks) after starting standard therapy using PET/CT

Description

Time Frame

4 months

Secondary Outcome Measure Information:

Title

Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.

Description

Describe fold changes in [18F]NOS uptake in patients who have a complete response or very good partial response vs patients who have a partial or no response to therapy at ~4 months.

Time Frame

4 months

Title

Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Description

Describe fold changes in [18F]NOS uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Time Frame

4 months

Title

Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Description

Describe fold changes in Florbetaben uptake in patients who have an NT-proBNP response at ~4 months vs patients who have no response or progression

Time Frame

4 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants will be at least 18 years of age Have an established diagnosis of AL amyloidosis based on standard criteria and planning to start systemic therapy. Have cardiac involvement as defined by all of the following: Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness at diastole >12mm in the absence of other causes (e.g. severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening NT-proBNP ≥ 650 pg/mL Participants should fall into 1 of the following 2 categories: Treatment-naïve or have completed no more than 1 cycle of initial therapy, OR Relapsed after 1 or more prior therapies, and at least 6 months from last treatment Have serum free light chain (FLC) differential (defined as amyloid-forming FLC minus non-amyloid-forming FLC) ≥ 50 mg/L. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures. Exclusion Criteria: Females who are pregnant or breast feeding at the time of the PET/CT scan will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential before the injection of radiotracer. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study Less than 6 months life expectancy as deemed by a treating physician

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Erin Schubert

Phone

215-573-6569

erinshu@pennmedicine.upenn.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paco Bravo

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Erin Schubert

Phone

215-573-6569

erinschu@pennmedicine.upenn.edu

12. IPD Sharing Statement

Learn more about this trial

Molecular Imaging of the Underlying Mechanism of Cardiotoxicity in Patients With Light Chain Amyloidosis Using PET/CT

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