Isatuximab for Primary Amyloidosis

Recruiting at 344 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Must not be taking: Doxycycline, Curcumin, Prednisone, others

Disqualifiers: Multiple myeloma, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 months

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have taken certain supplements or medications like doxycycline, curcumin, prednisone, dexamethasone, or EGCG within 14 days before joining the trial.

How is the drug Isatuximab unique for treating primary amyloidosis?

Isatuximab is unique because it is a monoclonal antibody that targets the CD38 protein on cells, which is different from many other treatments for primary amyloidosis. This drug is typically used for multiple myeloma, but its mechanism of action may offer a novel approach for treating primary amyloidosis, a condition with limited standard treatment options. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Isatuximab for treating primary amyloidosis?

While there is no direct data on Isatuximab for primary amyloidosis, similar drugs like Daratumumab, which also targets CD38 on plasma cells, have shown promising results in treating AL amyloidosis, with good responses in blood and organ function. ^{6 7 8 9 10}

Who Is on the Research Team?

Emma Scott

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with primary amyloidosis that has returned or isn't responding to treatment. They must not have taken certain anti-amyloidogenic substances recently, should be in relatively good health with a performance status of <=2, and have no severe allergies to monoclonal antibodies like isatuximab. Participants need functioning major organs, controlled blood pressure and diabetes, no HIV/AIDS complications, and cannot be pregnant or breastfeeding.

Inclusion Criteria

Your heart's pumping ability, measured by echocardiogram, is at least 35%.

Your doctor needs to confirm that you have a specific amount of disease and certain blood tests done before you can join the study.

Your blood test results must show a significant difference between two types of proteins in your blood within 14 days before joining the study.

Exclusion Criteria

Patient is living outside the US

I haven't had cancer in the last 5 years, except for skin cancer.

I have had a condition where my lymphocytes grow abnormally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab intravenously 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.

24 months

4 visits in the first month, 2 visits per month thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 6 months for up to 4 years.

4 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Isatuximab

Trial Overview The trial tests the effectiveness of Isatuximab—a type of monoclonal antibody—in patients with relapsed or refractory primary amyloidosis. It aims to see if this drug can stop cancer cells from growing and spreading. The study also includes laboratory biomarker analysis to monitor responses.

How Is the Trial Designed?

Group I: Treatment (isatuximab) Experimental Treatment 2 Interventions

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.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 49 patients with relapsed/refractory AL amyloidosis treated with daratumumab, the overall hematologic response rate was 81%, with 64% achieving a very good partial response or better, indicating strong efficacy in this challenging patient population.

Daratumumab was found to be safe and well tolerated, with no patients discontinuing treatment due to toxicity, and it demonstrated significant cardiac and renal responses (74% and 73%, respectively), supporting its use in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review. Shragai, T., Gatt, M., Lavie, N., et al.[2021]

The combination therapy of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (daratumumab-CyBorD) has become the new standard-of-care for systemic light chain (AL) amyloidosis, showing high rates of hematologic and organ response.

Recent advancements in patient selection and induction regimens have significantly reduced the mortality associated with autologous stem cell transplant (ASCT), while new treatments like venetoclax are proving effective for patients with specific genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. Palladini, G., Milani, P.[2023]

In a real-life study involving 33 patients with AL amyloidosis, daratumumab demonstrated good efficacy, achieving a 60% rate of favorable hematological responses and a 50% rate of organ responses.

The treatment was well-tolerated, indicating an acceptable toxicity profile, making daratumumab a promising option for patients with relapsed or refractory AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab in AL Amyloidosis: A Real-Life Experience of the "RTM" (Regional Tuscan Myeloma Network). Sammartano, V., Antonioli, E., Buda, G., et al.[2022]

Isatuximab, an anti-CD38 monoclonal antibody, significantly improves progression-free survival and tumor response when combined with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, based on phase III studies.

The combination therapies involving isatuximab were generally well tolerated, maintaining health-related quality of life and showing a manageable safety profile without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

Isatuximab is an IgG1 monoclonal antibody that targets CD38 on cancer cells and has been approved in the USA for treating multiple myeloma in patients who have undergone at least two prior therapies.

The approval of isatuximab, in combination with pomalidomide and dexamethasone, marks a significant advancement in treatment options for adult patients with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. Dhillon, S.[2021]

Isatuximab, a monoclonal antibody targeting CD38, was shown to significantly improve progression-free survival in adult patients with relapsed and refractory multiple myeloma when used in combination with pomalidomide and dexamethasone, compared to pomalidomide plus dexamethasone alone.

While treatment with isatuximab was associated with a higher incidence of treatment-related adverse events, including serious complications, the overall safety profile was deemed acceptable, leading to a positive benefit-risk ratio for its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. Delgado, J., Zienowicz, M., van Hennik, PB., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Teclistamab in relapsed or refractory AL amyloidosis, a multinational retrospective case series. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Daratumumab in AL amyloidosis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Daratumumab in AL Amyloidosis: A Real-Life Experience of the "RTM" (Regional Tuscan Myeloma Network). [2022]

6. France pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. [2021]

8. England pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Exposure-response analyses for selection/confirmation of optimal isatuximab dosing regimen in combination with pomalidomide/dexamethasone treatment in patients with multiple myeloma. [2022]