This study will test the hypothesis that in patients with previous daratumumab exposure, combination therapy of daratumumab, pomalidomide, and dexamethasone (DPd) will yield higher complete remission (CR) rates in relapsed/refractory amyloidosis than historical pomalidomide/dexamethasone treatment.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a commonly undiagnosed and potentially fatal disease. Contemporary studies on this condition often underrepresent the female gender and diverse patient populations. This registry retrospectively evaluated patients referred for 99mTc-pyrophosphate (PYP) Single Photon Emission Computed Tomography (SPECT) between 2014 and 2023 at Montefiore-Einstein in the Bronx. The patient population is racially and ethnically diverse and with a high proportion of females. Demographic, clinical (e.g.

This is a multicenter, open-label, Phase 3 study in up to approximately 1400 participants. Eligible participants will receive eplontersen once every 4 weeks for up to 36 months or 6 months after eplontersen is approved and available in the site's country, whichever occurs first. Participants will also receive daily supplemental doses of the recommended daily allowance (RDA) of vitamin A. This study will consist of the following periods: less than or equal to (≤) 10-week screening assessment period, up to 36-month treatment period, and up to 6-month post-treatment evaluation period.

The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM.

Study Rationale:

hATTR-PN is an inherited, progressive, fatal disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid fibrils predominantly in the peripheral nerves, heart, gastrointestinal tract, and other organs. hATTR-PN is a rare disease and there are no large epidemiological studies that reliably provide an indication of its prevalence. The worldwide distribution is unequal, with higher rates in Portugal, Japan, Brazil, Northern Sweden, and the US. Current estimates suggest there may be 10,000 afflicted patients worldwide.

This is a prospective, non-interventional, Long-term, multinational cohort safety study of patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy (hATTR-PN). The overarching goal of this study is to further characterize the long-term safety of TEGSEDI (inotersen) in patients with hATTR-PN under real-world conditions.

PRIMARY OBJECTIVES:

1. Test the safety and feasibility of isatuximab-based drug treatment.
2. Evaluate the preliminary efficacy of a slow-go approach in high risk AL amyloid patients.

STUDY TREATMENT

Each patient starts by receiving increasing intensity of treatment for AL Amyloidosis up to maximum tolerance, and then maintenance Isatuximab thereafter for a specified period.

This phase I trial studies the side effects of isatuximab and to see how well it works in treating patients with high risk immunoglobulin light chain amyloidosis (AL amyloidosis). Isatuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.

Primary light chain amyloidosis (AL) is the most common systemic amyloidosis, resulting from a plasma cell dyscrasia, a hematological malignancy. It causes a restrictive cardiomyopathy (AL-CMP) in over 70% of individuals. AL-CMP is as lethal as stage 4 lung cancer and more lethal than any other form of restrictive heart disease; if untreated, the mortality rate is 50% within 18 months.

Cardiac amyloidosis is a major cause of early treatment-related death and poor overall survival in individuals with systemic light chain amyloidosis. This project will develop a novel approach to visualize cardiac amyloid deposits using advanced imaging methods. The long-term goal of this work is to identify the mechanisms of cardiac dysfunction, in order to guide the development of novel life-saving treatments.

Despite rapidly advancing developments in targeted therapeutics and genetic sequencing, persistent limits in the accuracy and throughput of clinical phenotyping has led to a widening gap between the potential and the actual benefits realized by precision medicine. This conundrum is exemplified by current approaches to assessing morphologic alterations of the heart. If reliably identified, certain cardiac diseases (e.g. cardiac amyloidosis and hypertrophic cardiomyopathy) could avoid misdiagnosis and receive efficient treatment initiation with specific targeted therapies.

Despite rapidly advancing developments in targeted therapeutics and genetic sequencing, persistent limits in the accuracy and throughput of clinical phenotyping has led to a widening gap between the potential and the actual benefits realized by precision medicine.

Recent advances in machine learning and image processing techniques have shown that machine learning models can identify features unrecognized by human experts and more precisely/accurately assess common measurements made in clinical practice.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of venetoclax, MLN9708 (ixazomib citrate), and dexamethasone when used in combination.

II. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of venetoclax, MLN9708 (ixazomib citrate), and dexamethasone when used in combination.

SECONDARY OBJECTIVES:

This phase I/Ia trial finds the best dose and side effects of venetoclax given in combination with ixazomib citrate and dexamethasone in treating patients with light chain amyloidosis that has come back (relapsed) or does not respond to treatment (refractory) and who have an abnormal genetic change \[translocation t(11;14)\]. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ixazomib citrate is in a class of medications called proteasome inhibitors.

Transthyretin cardiac amyloidosis (ATTR-CA) causes progressive heart disease that is often overlooked. It harms the heart muscle because the unstable, unfurled amyloid proteins fold up into large pieces that get caught in between layers of heart tissue, causing amyloid deposits. The earlier it is detected, the better for the patient.

This is a single center, prospective cohort study that is evaluating the ability of 124I-evuzamitide PET scanning to detect potential therapeutic changes in subjects under treatment for ATTR after one year has elapsed since their original 124I-evuzamitide PET scan.

Ten previously scanned subjects will re-consent to undergo another 124I-evuzamitide PET scan. Demographic, clinical and phenotypic data will be collected to characterize potential changes since their previous scans.

The goal of this clinical trial is to learn about malnutrition and weight loss in patients with Amyloidosis.

The main question it aims to answer is:

Is it feasible to use a low-cost nutrition-based application (apps) for use on a smartphone to obtain detailed information on caloric intake in Amyloidosis patients

Participants will be asked to: