124I-Evuzamitide for Amyloidosis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Oregon Health and Science University
Must not be taking: Heparin, Heparin analogs
Disqualifiers: Severe claustrophobia, Dialysis, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a single center prospective study evaluating 124I-evuzumitide in patients with systemic amyloidosis. The purpose of this study is to 1)identify and characterize the distribution and uptake of 124I-evuzumitide in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and 2) Correlate the uptake with the structure and function of different organs, including the heart. To achieve these goals, eligible patients will undergo primarily hybrid positron emission tomography and magnetic resonance imaging (PET/MRI). In a subgroup of patients who are unable to undergo PET/MR, computed tomography will be used instead of MRI (i.e. PET/CT). In a subgroup of patients, repeat imaging with the same modality will be done at a interval of 6-12 months. Clinically available data (demographics, phenotype, imaging, laboratory) will also be collected to characterize the disease in each patient.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications, but you should not have received heparin or similar medications within 7 days before the study drug is given.
What data supports the effectiveness of the drug 124I-Evuzamitide for treating amyloidosis?
Research on similar treatments, like iodine-131 tositumomab, shows that radioimmunotherapy can be effective in treating certain types of lymphoma, with some patients experiencing long-lasting remissions. This suggests that using a similar approach with 124I-Evuzamitide might also be effective for amyloidosis, although direct evidence for this specific condition is not provided.
12345How does the drug 124I-Evuzamitide differ from other treatments for amyloidosis?
124I-Evuzamitide is unique because it is a radiotracer that can bind to amyloid deposits from multiple types of amyloid proteins, allowing for non-invasive and quantitative detection of amyloid throughout the body using PET/CT imaging. This approach is novel compared to traditional methods, which often rely on indirect measurements and are less effective in early diagnosis and monitoring of amyloidosis.
678910Eligibility Criteria
This trial is for people with systemic amyloidosis, specifically those who have a mutation in the transthyretin gene and known organ involvement. It's also open to patients with multiple myeloma or monoclonal gammopathy of undetermined significance. People can't join if they're allergic to potassium iodide or gadolinium, have severe kidney issues, recently used heparin products, or can't complete imaging procedures due to claustrophobia or other conditions.Inclusion Criteria
I have been diagnosed with multiple myeloma.
Patient willing to consent for the study and undergo the study procedures
I carry a mutation in the transthyretin gene.
+2 more
Exclusion Criteria
You are allergic to potassium iodide or gadolinium.
I am on dialysis or my kidney function is very low.
You have extreme fear of enclosed spaces or any medical condition that would make it difficult for you to complete the imaging tests.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Imaging
Participants undergo hybrid 124I-Evuzamitide PET/MRI imaging (or PET/CT) to evaluate distribution and uptake
1 day
1 visit (in-person)
Follow-up Imaging
In a subgroup of patients, repeat imaging with the same modality will be done at an interval of 6-12 months
6-12 months
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after imaging
4 weeks
Participant Groups
The study is testing how well Iodine-124 Evuzumitide (AT-01) shows up in different organs of patients with amyloidosis using advanced imaging techniques like PET/MRI scans. Some may get PET/CT scans instead. The goal is to see where the drug goes in the body and how it relates to heart structure and function over time.
1Treatment groups
Experimental Treatment
Group I: Patients with ATTR-CMExperimental Treatment1 Intervention
Patients with ATTR-CM will undergo hybrid 124I-Evuzamitide PET/MRI imaging (or PET/CT) at baseline and in a subgroup, repeat imaging will be performed at an interval of 6-12 months.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Oregon Health & Science UniversityPortland, OR
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Who Is Running the Clinical Trial?
Oregon Health and Science UniversityLead Sponsor
Attralus, Inc.Industry Sponsor
References
Iodine-131 anti-B1 antibody for B-cell lymphoma: an update on the Michigan Phase I experience. [2019]Iodine-131 anti-B1 antibody radioimmunotherapy for B-cell lymphoma was previously reported to have substantial antitumor activity in B-cell non-Hodgkin's lymphoma (NHL) after failures of standard and salvage chemotherapy. In this article, the University of Michigan Phase I clinical experience is updated, with follow-up of up to 6 yr since initial treatment reported.
Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma. [2019]To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
Tositumomab and iodine [131I] tositumomab in the management of follicular lymphoma. An oncologist's view. [2019]Iodine [(131)I] tositumomab, administered in combination with unlabelled tositumomab, is a novel radioimmunotherapeutic regimen that targets the CD20 antigen present on normal and malignant B-cells. The efficacy and safety of the non-myeloablative regimen has been demonstrated in follicular and transformed follicular lymphoma over the last decade in a series of clinical studies, culminating in FDA approval in June 2003. In patients with relapsed or refractory disease some remissions have proven to be durable, and frequently longer in duration than previously administered chemotherapeutic agents. As initial therapy for advanced stage follicular lymphoma, response rates are particularly impressive. Toxicity has been principally haematological, with a single nadir at 4-6 weeks post-therapy. Administration is free of many of the side effects of conventional chemotherapy, although concerns about the long term risk of therapy related myelodysplasia persist. The challenge now comes from deciding the correct place of iodine [(131)I] tositumomab in treatment algorithms for follicular and other ''indolent'' lymphomas. Sequential administration after chemotherapy is being actively investigated, as is its role in myeloablative therapy. Issues of cost-benefit aside, it is a significant development in the therapy of these ''chronic'' malignancies.
Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma. [2017]Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7.
Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. [2021]CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P =.005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)
Production of monoclonal antibody against amyloid fibril protein and its immunohistochemical application. [2015]An autopsy case of multiple myeloma (IgA-lambda) with extensive amyloid arthropathy of the systemic joints was described. Heavy deposits of amyloid (amyloidoma) were observed in the articular cavities of the joints. Furthermore, numerous amyloid deposits were found in the walls of small blood vessels in the general organs. Incubation of the paraffin sections of amyloid with potassium permanganate produced little loss of Congo red affinity and apple-green birefringence under polarized light. A crude preparation of amyloid protein was isolated from a frozen intra-articular mass, which had been obtained at necropsy, and injected into the footpads of BALB/c mice with complete Freund's adjuvant. The immune spleen cells were fused with myeloma cells (P3 X 63-Ag8.653) under the presence of polyethylene glycol. Hybridoma cell lines, producing supernatants which reacted not only with amyloid substances but also with normal human tissues, were omitted from the subjects of recloning, and one hybridoma cell line (Am-1) producing a specific monoclonal antibody (MAb) against the immunized amyloid substance was finally obtained. Using the indirect immunoperoxidase method, the specificity of MAb Am-1 was confirmed in the cryostat sections as well as in the formalin-fixed paraffin sections of various organs of the case from which the crude amyloid protein was obtained and used for immunization. Amyloid deposits in 25 cases with amyloidosis or amyloid deposits were examined with MAb Am-1, and 2 cases showed positive reactivity with Am-1. These 2 cases presented primary amyloidosis and focal amyloid deposits in the oral cavity, respectively; Congo red staining of amyloid in these cases showed resistance to treatment with potassium permanganate, as observed in the amyloid of the original case used for immunization. Trypsin treatment of the sections resulted in a loss of positive reactivity with MAb Am-1 in all these cases. This result indicates that Am-1 recognizes a substance composed of protein molecules. Furthermore, the immunohistochemical distribution of Am-1 positive reaction was consistent with the histological distribution of substance which could be stained by Congo red and showed apple-green birefringence under polarized light. These results have suggested that Am-1 reacts with a portion of amyloid protein which is resistant to treatment with potassium permanganate followed by Congo red staining.
First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14-a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging. [2022]Label="PURPOSE">Accurate diagnosis of amyloidosis remains a significant clinical challenge and unmet need for patients. The amyloid-reactive peptide p5+14 radiolabeled with iodine-124 has been developed for the detection of amyloid by PET/CT imaging. In a first-in-human evaluation, the dosimetry and tissue distribution of 124I-p5+14 peptide in patients with systemic amyloidosis. Herein, we report the dosimetry and dynamic distribution in the first three enrolled patients with light chain-associated (AL) amyloidosis.
Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. [2021]Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.
Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide 124I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging. [2023]There are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable patient outcomes. The ability to non-invasively and quantitatively detect amyloid throughout the body, even in at-risk populations, before clinical manifestation would be invaluable. To this end, a pan-amyloid-reactive peptide, p5+14, has been developed that is capable of binding all types of amyloid. Herein, we demonstrate the ex vivo pan-amyloid reactivity of p5+14 by using peptide histochemistry on animal and human tissue sections containing various types of amyloid. Furthermore, we present clinical evidence of pan-amyloid binding using iodine-124-labeled p5+14 in a cohort of patients with eight (n = 8) different types of systemic amyloidosis. These patients underwent PET/CT imaging as part of the first-in-human Phase 1/2 clinical trial evaluating this radiotracer (NCT03678259). The uptake of 124I-p5+14 was observed in abdominothoracic organs in patients with all types of amyloidosis evaluated and was consistent with the disease distribution described in the medical record and literature reports. On the other hand, the distribution in healthy subjects was consistent with radiotracer catabolism and clearance. The early and accurate diagnosis of amyloidosis remains challenging. These data support the utility of 124I-p5+14 for the diagnosis of varied types of systemic amyloidosis by PET/CT imaging.
Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study. [2023]Label="BACKGROUND">Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. 124I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins. Its ability to quantify cardiac amyloid has not yet been investigated.