Brief Summary

This phase II trial studies how well isatuximab works in treating patients with primary amyloidosis that has come back or does not respond to treatment. Monoclonal antibodies, such as isatuximab, may interfere with the ability of cancer cells to grow and spread.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Jun 2018

Longer than P75 for phase_2

Geographic Reach

1 country

345 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.3 years study duration

First Submitted

Initial submission to the registry

April 9, 2018

Completed

8 days until next milestone

First Posted

Study publicly available on registry

April 17, 2018

Completed

2 months until next milestone

Study Start

First participant enrolled

June 6, 2018

Completed

5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2023

Completed

20 days until next milestone

Study Completion

Last participant's last visit for all outcomes

September 19, 2023

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

February 27, 2025

Completed

Last Updated

September 9, 2025

Status Verified

February 1, 2025

Enrollment Period

5.2 years

First QC Date

April 9, 2018

Results QC Date

December 9, 2024

Last Update Submit

September 2, 2025

Conditions

Amorphous, Eosinophilic, and Acellular Deposit Constipation Diarrhea Early Satiety Gastrointestinal Hemorrhage Hepatomegaly Lymphadenopathy Macroglossia Nausea Primary Systemic Amyloidosis Purpura Recurrent Primary Amyloidosis Refractory Primary Amyloidosis

Outcome Measures

Primary Outcomes (1)

Assess Efficacy by Confirmed Overall Hematologic Response
To assess the efficacy as measured by the confirmed overall hematologic response rate (partial response, very good partial response, complete response) of isatuximab in relapsed/ refractory systemic light chain (AL) amyloidosis. Measured as rate of partial response or better. Partial response is defined as a dFLC decrease of ≥ 50%, but remaining \> 4.0 mg/dL. Very good partial response is defined as the difference between involved and uninvolved FLCs \[dFLC\] \< 4.0 mg/dL. Complete response is defined as laboratory values within the normal range free light chain (FLC) ratio (0.25 - 1.65) and negative serum and urine immunofixation.
From date of enrollment until progression or death due to any cause, whichever occurs first, assessed up to 4 years

Secondary Outcomes (5)

To Evaluate Toxicities in the Treatment of Relapsed/Refractory AL Amyloidosis With Isatuximab.
From date of enrollment until progression or death due to any cause, whichever occurs first, assessed up to 4 years
Overall Survival (24 Month Estimate)
From date of enrollment up to 2 years
Duration of Response (24 Month Estimate)
Up to 2 years
Time to Hematologic Response
From registration to time of confirmed hematologic progression
Progression-free Survival (24 Month Estimate)
From registration to time of confirmed hematologic progression

Study Arms (1)

Treatment (isatuximab)

EXPERIMENTAL

Patients receive isatuximab IV on days 1, 8, 15, and 22 of course 1 and on days 1 and 15 of subsequent courses. Treatment repeats every 28 days for 24 courses in the absence of disease progression or unacceptable toxicity.

Biological: IsatuximabOther: Laboratory Biomarker Analysis

Interventions

IsatuximabBIOLOGICAL

Given IV

Also known as: Hu 38SB19, SAR 650984, SAR650984

Treatment (isatuximab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (isatuximab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patient must have relapsed or refractory primary systemic AL amyloidosis, histologically-confirmed by positive Congo red stain with green by birefringence on polarized light microscopy, OR characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence)
Patient must have measurable disease within 28 days prior to registration; serum beta2 microglobulin, serum quantitative immunoglobulins (immunoglobulin \[Ig\]G, IgA, and IgM), serum free kappa and lambda, and serum protein electrophoresis (SPEP) with M-protein quantification must be obtained within 14 days prior to registration
Patient must demonstrate a difference in the involved serum free light chains (kappa or lambda) versus the uninvolved serum free light chain of \>= 4.5 mg/dL within 14 days prior to registration
Patient must have objective organ involvement defined by ONE (or more) of the following; all disease for involved organs must be assessed and documented on the AL baseline tumor assessment form
Kidney: albuminuria greater than or equal to 500 mg per day on a 24-hour urine specimen within 35 days prior to registration, OR prior kidney biopsy (at time of diagnosis) showing amyloid deposition
Heart: mean left ventricular wall thickness on echocardiogram greater than or equal to 12 mm in the absence of hypertension or valvular heart disease, OR N-terminal fragment brain natriuretic protein (NT-pro) brain natriuretic peptide (BNP) greater than 332 ng/mL provided that patient does not have impaired renal function (as defined by calculated creatinine clearance less than 25 mL/min) within 14 days prior to registration, OR prior cardiac biopsy (at time of diagnosis) showing amyloid deposition with past documented or presently noted clinical symptoms and signs supportive of a diagnosis of heart failure in the absence of an alternative explanation for heart failure
Liver: hepatomegaly (total liver span \> 15 cm) as demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI) within 35 days prior to registration OR elevated alkaline phosphatase (ALP) greater than 1.5 times the upper limit of normal within 14 days prior to registration, OR prior liver biopsy (at time of diagnosis) showing amyloid deposition
Gastrointestinal tract: prior biopsy showing amyloid deposition AND symptoms such as GI bleeding or persistent diarrhea (\> 4 loose stools/day on most days over a consecutive 28-day period)
Autonomic or peripheral nervous system: orthostatic blood pressure, symptoms of nausea, early satiety, diarrhea or constipation, abnormal sensory and/or motor findings on neurologic exam, or gastric atony by gastric emptying scan; Note: pulse and blood pressure must be recorded with the patient supine (lying down), and then again after at least 1 minute, but less than 3 minutes of standing; this assessment must be repeated on 2 separate occasions (at least 1 day apart; e.g. day -3 and day -1) within a 28-day screening period
Soft tissue: macroglossia, or soft tissue deposits (including lymphadenopathy, recurrent peri-orbital purpura, peri-articular, skin or other soft tissue) requiring therapy
Patients must not have active symptomatic multiple myeloma, as defined by 2015 International Myeloma Working Group (IMWG) criteria (hypercalcemia, renal failure, anemia, and bone \[CRAB\] criteria; bone marrow plasmacytosis \> 60%); kappa: lambda ratio \> 100 is acceptable only if the clinical symptoms and sign are attributable only to amyloidosis and not multiple myeloma (hemoglobin \[Hgb\] \< 8 g/dL)
Patient must be relapsed or refractory to at least one prior line of therapy (such as: transplant, radiation, or chemotherapy)
Patients must have completed other systemic therapy \>= 14 days or investigational drug \>= 28 days prior to registration, surgery (other than biopsies) \>= 21 days prior to registration, and any autologous stem cell transplant (ASCT) \>= 100 days prior to registration
Patients must not have received any or supplements which have been known to have some anti-amyloidogenic effect (such as: doxycycline; curcumin; prednisone; dexamethasone; epigallocatechin gallate \[EGCG\]) within 14 days prior to registration
Patients must not have any known allergies to isatuximab or other monoclonal antibody therapies
+25 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (345)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC