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Isatuximab as Upfront Therapy for the Treatment of High Risk AL Amyloidosis | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1

Isatuximab as Upfront Therapy for the Treatment of High Risk AL Amyloidosis

Slow-Go Strategy for High Risk AL Amyloidosis: Isatuximab for Upfront Therapy

NCT04754945•Emory University

Summary

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.

Detailed Description

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. All patients will receive Isatuximab (weekly x 4 then every other week) plus dexamethasone 4 mg PO/IV days weekly. If tolerating Isatuximab/Dex4 (earliest time to escalate C1D15), add Velcade to 1 mg/m2 SQ weekly. If tolerating Isa/Vel1.0/Dex4 (earliest time to escalate C2D1), increase dexamethasone to 12 mg weekly. If tolerating Isa/Velcade1.0/Dex12 (earliest time to escalate C3D1), increase Velcade to 1.3 mg/m2 SQ. If tolerating Isa/Velcade1.3/Dex12 (earliest time to escalate C4D1), add cyclophosphamide 300 mg IV weekly. If tolerating Isa/Velcade1.3/Cy300/Dex12 (earliest time to escalate C5D1), increase cyclophosphamide to 400 mg IV weekly. If tolerating Isa/Velcade1.3/Cy400/Dex12 (earliest time to escalate C6D1), increase cyclophosphamide to 500 mg IV weekly. Tolerance determined by the patient not reaching an escalation limiting toxicity AND patient approval to dose escalate. Patients then receive dexamethasone and isatuximab as maintenance treatment twice per month for 12 months in the absence of disease progression or unacceptable toxicity.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry (IHC) and polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens in an organ other than bone marrow, characteristic electron microscopy appearance, or mass spectrometry. Specifically for male subjects 70 years of age or older who have cardiac involvement only and subjects of African descent, mass spectrometry typing of AL amyloid in a tissue biopsy is recommended to rule out other types of amyloidosis such as age-related amyloidosis or hereditary amyloidosis (ATTR mutation)
•Must have evidence of high risk AL amyloidosis defined as one of the following any time within the 6 months prior to consent:
•* Biomarker-based indicators of severe disease: NT-proBNP \> 8500 ng/L OR hs-cTnT \>= 50 ng/L
•* BUMC 2019 stage 3b requiring both TnI \> 0.1 ng/mL and BNP \> 700 pg/mL
•* Mayo 2012 stage 4 that includes each of the following a) cTnT \>= 0.025 ng/mL or hs-cTnT \>= 40 ng/mL; b) NT-proBNP \>= 1800 pg/mL; and c) dFLC \>= 180 mg/L
•* Significant AL amyloid related hypotension (systolic blood pressure \[SBP\] \< 100 mm Hg or symptomatic orthostatic hypotension defined as a decrease in systolic blood pressure upon standing of \> 20 mm Hg despite medical management \[fludrocortisone, midodrine, etc\] in the absence of volume depletion)
•Absolute neutrophil count (ANC) \>= 1000/uL
•Platelet count \>= 50,000 and platelet transfusion independent for 1 week prior to screening
•Estimated creatinine clearance \>= 20 mL/min/1.73 m\^2 as defined by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)
•Total bilirubin \< 1.5 x institutional upper limit of normal (IULN) except for patients with Gilbert syndrome in which case total bilirubin =\< 2 x IULN
+5 more criteria

Exclusion Criteria

•\> 1 prior line of therapy
•Refractory to any proteasome inhibitor
•Prior CD38 antibody exposure
•Cardiac exclusions:
•* Subjects with a history of sustained ventricular tachycardia EXCEPT in patients with a pacemaker/implantable cardioverter defibrillator (ICD)
•* Baseline QT interval as corrected by institutional rate correction algorithm (e.g. corrected QT interval by Bazett formula \[QTc\]B or corrected QT interval by Fridericia formula \[QTcF\]) \> 500 msec EXCEPT in patients with a pacemaker
•Grade 2 or greater peripheral sensory neuropathy
•Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer
•Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
•Human immunodeficiency virus (HIV) positive EXCEPT if the patient meets all the following: CD4 \> 350 cells/mm3, undetectable viral load, maintained on modern therapeutic regimen utilizing non CYP interacting agents (e.g. excluding ritonavir), and no untreated acquired immune deficiency syndrome defining opportunistic infections
+8 more criteria

Locations (6)

University of California

Orange, California, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Columbia University

New York, New York, United States

UT Southwestern

Dallas, Texas, United States

Key Dates

Start Date

April 28, 2021

Primary Completion Date

May 6, 2026

Completion Date

July 24, 2026

Last Updated

February 18, 2026

Enrollment

ACTUAL participants

Conditions

AL Amyloidosis

Interventions

Bortezomib

DRUG

Cyclophosphamide

DRUG

Dexamethasone

DRUG

Isatuximab

BIOLOGICAL

Optimize First-line Treatment for AL Amyloidosis With t (11; 14)

NCT06192979

Amyloidosis; SystemicAL Amyloidosis

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RECRUITINGPHASE1

Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis

NCT07250269

Relapsed/Refractory AL Amyloidosis

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RECRUITING

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 18, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Isatuximab as Upfront Therapy for the Treatment of High Risk AL Amyloidosis

Inclusion Criteria

Exclusion Criteria

Optimize First-line Treatment for AL Amyloidosis With t (11; 14)

Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis

A Registry of AL Amyloidosis (ReAL)

Isatuximab Plus Pomalidomide and Dexamethasone Association for Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy

National Registry of Rare Kidney Diseases

Multimodal Radiomics Model (18F-FAPI PET/CT + CMR) for AL Cardiac Amyloidosis Prognosis