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64Cu-LLP2A for Imaging Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

64Cu-LLP2A

PET/MR

Blood samples for serum stability

Blood samples for metabolite analysis

Urine sample

Tumor biopsy

Electrocardiogram

PET/CT

About this trial

This is an interventional diagnostic trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Adult patients 18 years of age or older with clinically or pathologically defined MM in accordance with International Myeloma Working Group or as stated in office note / clinical assessment from treating physician.
*All types of active myeloma are eligible including both newly diagnosed and previously treated provided plans are to start a new treatment or restart a prior treatment.
Healthy Volunteer Subjects: Adult 18 years of age or older with no known hematologic disorder such as anemia, leukemia, etc. who is considered healthy based on assessment by PI. (Cohort 1 only).
Able to give informed consent.
Does not have any exclusions related to PET/MR imaging: No implanted medical devices such as: pacemaker, defibrillator, neurostimulator, artificial heart valve, cerebral aneurysm clips, no accidental exposure to metal fragments (if applicable)
If applicable for administration of contrast with MRI imaging subject must have a calculated GFR of at least 60 mg/mL/1.73 m^2.
Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post-menopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 64Cu-LLP2A) is negative.

Exclusion Criteria:

Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years.
Unable to tolerate up to 90 min of PET/MR or PET/CT imaging per imaging session.

Sites / Locations

Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1: Pilot 64Cu-LLP2A Imaging

Cohort 2: Quantitative 64Cu-LLP2A Imaging

Arm Description

16 adult individuals (6-8 patients with known MM; 6-10 healthy volunteers) All subjects who enter the study in Cohort 1 will be injected with up to 11 mCi of 64Cu-LLP2A and will undergo body imaging at least twice within 0-30 hrs following administration of 64Cu-LLP2A to study tracer biodistribution and calculate human dosimetry 6 subjects will also undergo dynamic study for 60 mins immediately after administration of 64Cu-LLP2A.

20 patients with MM will be recruited Subjects who enter on study in Cohort 2 will undergo a 60-min dynamic imaging over the known site of disease (OR pelvis and lower lumbar spine, if no site of disease is known). Following a simple DIXON MRI or low dose CT scan for attenuation correction, subjects will be injected with a dose of up to11 mCi of 64Cu-LLP2A and a list mode dynamic imaging acquisition will begin for a total of 60 mins. Following the dynamic study, or at the optimal time point determined from cohort 1 imaging, after a simple DIXON or low dose CT scan for body (top of the head to below the knees) attenuation correction, emission scans (2-5 min per bed position) will be performed

Outcomes

Primary Outcome Measures

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by average organ activity concentration of 64Cu-LLP2A

-Average organ activity concentration will be measured and decay corrected by utilizing regions of interest (ROIs) drawn around all organs visible on 64Cu-LLP2A images. Activity organ residence times will be calculated by numerical or analytical integration of the time-activity curves. Uptake/clearance functional fits of mono or bi-exponential functions will be performed and analytical integration, accounted for physical delay, will be performed. The calculated residence times will be used with the program OLINDA/EXM for 64Cu and using the adult human (male/femal) model to calculate the individual organ radiation dose, the whole-body dose, and the effective dose

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the number of participants who experience an adverse event related to 64Cu-LLP2A

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the optimal image time after injection of 64Cu-LLP2A

-The optimal imaging time after injection yields the best image quality and tumor-to-non-tumor ratio for visual and quantitative analysis of the lesions

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by image quality of 64Cu-LLP2A-PET/MR images

Overall PET image quality will be graded visually (using 4-point scale with 1 being the worst and poor quality, not acceptable for diagnostic interpretation and 4 being good image quality, similar to routine clinical studies). The images will be assessed by independent observers (a nuclear medicine expert in evaluating PET images using novel radiotracers, and a MR radiologist expert in evaluating MR images The images will then be correlated to MRI (and biopsy if available) to assess whether the lesions identified on 64Cu-LLP2A correspond to myeloma lesions

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by lesion detection of 64Cu-LLP2A-PET/MR images

-Lesion detection is measured by lesion uptake in comparison with the surrounding tissue

Secondary Outcome Measures

Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical stage

-SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to overall clinical stage as a way to compare accuracy of imaging to known clinical stage

Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical tumor measurement of tumor burden as measured by M-protein of myeloma

SUVmax is a mathematical measurement of tumor burden seen on images and calculated by the following equation SUVmax= r / (a'/w) where r= radioactivity concentration in tumor (kBq/ml) as measured by the PET scanner within a defined region of interest, a'=the decay corrected amount of injected 64Cu-LLP2A and w= weight of the patient in grams When PET imaging shows uptake of 64Cyu-LLP2A in site(s) of known tumor the SUVmax will be compared to clinical measurement of tumor burden as seen by the laboratory values for M-protein (lab measurement for myeloma gamma globulin which is increased in multiple myleom due to an abnormal monoclonal proliferation of plasma cells)

Comparision of tumor burden (SUVmax) of 64Cu-LLP2A to clinical measurement of tumor burden as measured by the plasma cell fraction within the bone marrow

Hierarchical models will be used to estimate the correlation of SUVmax with M-protein expression Variance components models will be fit to identify component (proportion) of total variance

Full Information

NCT ID

NCT03804424

First Posted

December 10, 2018

Last Updated

July 30, 2023

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT03804424

Brief Title

64Cu-LLP2A for Imaging Multiple Myeloma

Official Title

Early Phase I Evaluation of 64Cu-LLP2A for Imaging Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 20, 2018 (Actual)

Primary Completion Date

November 30, 2024 (Anticipated)

Study Completion Date

November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The investigators are performing a trial with goals to demonstrate the feasibility of imaging multiple myeloma (MM) patients with 64Cu-LLP2A-positron emission tomography (PET)/magnetic resonance (MR). The investigators suggest that 64Cu-LLP2A will allow for an accurate molecular imaging of MM lesions, which will have an important impact on early stage disease detection and in the long term on the initiation and choice of therapy in these patients.

6. Conditions and Keywords

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

Multiple Myeloma

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Early Phase 1

Interventional Study Model

Sequential Assignment

Masking

Investigator

Masking Description

Images will be assessed by independent observers (nuclear medicine expert in evaluating PET images using novel radiotracers, and MR radiologist expert in evaluating MR images), who will initially be blinded to all clinical information available (such as tumor size and location), which will be followed by un-blinded combined reading of the PET and MR images

Allocation

Non-Randomized

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1: Pilot 64Cu-LLP2A Imaging

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2: Quantitative 64Cu-LLP2A Imaging

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

64Cu-LLP2A

Intervention Description

-64Cu-LLP2A, will be manufactured following batch production record at the cyclotron GMP facility (Washington University School of Medicine GMP radiochemistry/cyclotron facility)

Intervention Type

Device

Intervention Name(s)

PET/MR

Intervention Description

-All PET imaging will be performed as PET/MR or PET/CT

Intervention Type

Procedure

Intervention Name(s)

Blood samples for serum stability

Intervention Description

-3 venous samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (2 mL each) will be obtained at the following time points: Cohort 1: prior to injection, at completion of dynamic scanning in those who undergo dynamic imaging and at completion of one of the body imaging time points. In those who do not undergo dynamic imaging, prior to injection, and after completing body imaging at 2 of the 3 time points. Cohort 2: subjects will have samples drawn prior to injection, at completion of dynamic scanning, and at completion of body imaging.

Intervention Type

Procedure

Intervention Name(s)

Blood samples for metabolite analysis

Intervention Description

-Typically, 2 blood samples obtained from an IV site separate from the site of 64Cu-LLP2A injection (preferably 1 within the first 5 min and 1 at the completion of the first hour of imaging) will be obtained.

Intervention Type

Procedure

Intervention Name(s)

Urine sample

Intervention Description

-Cohort 1 only

Intervention Type

Procedure

Intervention Name(s)

Tumor biopsy

Intervention Description

-Cohort 2 only and only if there hasn't been a recent biopsy of disease

Intervention Type

Procedure

Intervention Name(s)

Electrocardiogram

Other Intervention Name(s)

ECG

Intervention Description

-A standard 12-lead ECG will be obtained on all subjects at baseline (within 30 mins prior to injection of 64Cu-LLP2A), and at least 60 minutes post injection or prior to study discharge

Intervention Type

Device

Intervention Name(s)

PET/CT

Intervention Description

-All PET imaging will be performed as PET/MR or PET/CT

Primary Outcome Measure Information:

Title

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by average organ activity concentration of 64Cu-LLP2A

Description

Time Frame

Up to 30 hours after imaging

Title

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the number of participants who experience an adverse event related to 64Cu-LLP2A

Description

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Time Frame

Through 48 hours after last administration of 64Cu-LLP2A (estimated to be at most 4 days)

Title

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by the optimal image time after injection of 64Cu-LLP2A

Description

-The optimal imaging time after injection yields the best image quality and tumor-to-non-tumor ratio for visual and quantitative analysis of the lesions

Time Frame

Up to 30 hours after imaging

Title

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by image quality of 64Cu-LLP2A-PET/MR images

Description

Time Frame

Up to 30 hours after imaging

Title

Feasibility of imaging MM patients with 64Cu-LLP2A-PET/MR as measured by lesion detection of 64Cu-LLP2A-PET/MR images

Description

-Lesion detection is measured by lesion uptake in comparison with the surrounding tissue

Time Frame

Up to 30 hours after imaging

Secondary Outcome Measure Information:

Title

Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical stage

Description

Time Frame

Up to 30 hours after imaging

Title

Comparison of tumor burden (SUVmax) of 64Cu-LLP2A to clinical tumor measurement of tumor burden as measured by M-protein of myeloma

Description

Time Frame

Up to 30 hours after imaging

Title

Comparision of tumor burden (SUVmax) of 64Cu-LLP2A to clinical measurement of tumor burden as measured by the plasma cell fraction within the bone marrow

Description

Hierarchical models will be used to estimate the correlation of SUVmax with M-protein expression Variance components models will be fit to identify component (proportion) of total variance

Time Frame

Up to 30 hours after imaging

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients 18 years of age or older with clinically or pathologically defined MM in accordance with International Myeloma Working Group or as stated in office note / clinical assessment from treating physician. *All types of active myeloma are eligible including both newly diagnosed and previously treated provided plans are to start a new treatment or restart a prior treatment. Healthy Volunteer Subjects: Adult 18 years of age or older with no known hematologic disorder such as anemia, leukemia, etc. who is considered healthy based on assessment by PI. (Cohort 1 only). Able to give informed consent. Does not have any exclusions related to PET/MR imaging: No implanted medical devices such as: pacemaker, defibrillator, neurostimulator, artificial heart valve, cerebral aneurysm clips, no accidental exposure to metal fragments (if applicable) If applicable for administration of contrast with MRI imaging subject must have a calculated GFR of at least 60 mg/mL/1.73 m^2. Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post-menopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 64Cu-LLP2A) is negative. Exclusion Criteria: Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years. Unable to tolerate up to 90 min of PET/MR or PET/CT imaging per imaging session.

Central Contact Person:

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

Farrokh Dehdashti, M.D.

Phone

314-362-1474

dehdashtif@wustl.edu

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

Jennifer Frye, CNMT, CCRC

Phone

314-747-1604

fryej@wustl.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Farrokh Dehdashti, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Farrokh Dehdashti, M.D.

Phone

314-362-1474

dehdashtif@wustl.edu

First Name & Middle Initial & Last Name & Degree

Jennifer Frye, CNMT, CCRC

Phone

314-747-1604

fryej@wustl.edu

First Name & Middle Initial & Last Name & Degree

Farrokh Dehdashti, M.D.

First Name & Middle Initial & Last Name & Degree

Ravi Vij, M.D.

First Name & Middle Initial & Last Name & Degree

Korresh Shoghi, Ph.D.

First Name & Middle Initial & Last Name & Degree

Richard Laforest, Ph.D.

First Name & Middle Initial & Last Name & Degree

Amber Salter, Ph.D.

First Name & Middle Initial & Last Name & Degree

Tyler Fraum, M.D.

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

A primary means of sharing data will be through publication in peer-reviewed journals. As required by the NIH Public Access Policy, the investigators will submit to the NIH National Library of Medicine's PubMed Central an electronic version of final manuscripts upon acceptance for publication, resulting from research supported by these funds, in whole or in part, with direct costs from NIH. It is expected that approximately 1-2 presentations at national meetings Early phase I evaluation of 64Cu-LLP2A for imaging multiple myeloma will generate imaging, safety and dosimetry data from PET/CT and MR studies of 64Cu-LLP2A. Serum markers such as M-protein, plasma cell density and immunohistochemistry will be correlated with imaging, in order to understand the interaction of 64Cu-LLP2A with VLA-4 in vivo. It is the explicit intention that these data will be placed in a readily accessible public database.

IPD Sharing Time Frame

All efforts will be made to rapidly release data through publications of the results as quickly as it is possible to analyze the experiments.

Links:

URL

http://www.siteman.wustl.edu

Description

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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64Cu-LLP2A for Imaging Multiple Myeloma

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