Isatuximab for Primary Amyloidosis

No longer recruiting at 347 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of isatuximab, a monoclonal antibody, for individuals with primary amyloidosis—a condition where abnormal protein accumulates in organs—who have not responded to previous treatments. The trial aims to determine if this drug can halt disease progression. It suits those whose amyloidosis has returned or is unresponsive to other therapies and who have organ issues like heart, kidney, or liver problems related to the disease. Participants will receive the treatment in cycles and will be monitored for changes in their condition. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that isatuximab is likely to be safe for humans?

Research has shown that isatuximab is generally well-tolerated by patients with AL amyloidosis. One study found that isatuximab effectively treated patients whose disease had returned or was not responding to other treatments, indicating positive reactions in patients' blood and organs. Another study reported that isatuximab is as safe as other treatments targeting the CD38 protein on cancer cells.

These findings suggest that isatuximab is relatively safe for use in this context, though, like any treatment, it might have side effects. Some patients may experience mild to moderate reactions, but serious side effects are uncommon. For those considering joining a trial, these results are promising for the safety of isatuximab. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Isatuximab is unique because it targets a specific protein called CD38 on the surface of abnormal plasma cells, which are involved in primary amyloidosis. Unlike traditional treatments, which often include chemotherapy or corticosteroids, isatuximab acts as an immunotherapy, harnessing the body's immune system to attack these cells. Researchers are excited about isatuximab because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes for patients with this condition.

What evidence suggests that isatuximab might be an effective treatment for primary amyloidosis?

Research has shown that isatuximab, the treatment under study in this trial, may help treat primary amyloidosis, particularly in patients whose condition has returned or hasn't responded to other treatments. In earlier studies, about 77% of patients showed improvement in their illness, with some experiencing positive changes in just over a month. This treatment uses monoclonal antibodies, which are special proteins that target and disrupt harmful cells. Overall, evidence suggests that isatuximab could be a good option for those facing challenging cases of primary amyloidosis. ^{1 2 6 7 8}

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 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 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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3378/533919/Isatuximab-in-Relapsed-AL-Amyloidosis-Results-of-a

Isatuximab in Relapsed AL Amyloidosis: Results of a ... The overall hematologic response rate was 77.1% with a rapid median time to partial response or better of 1.1 months. Two patients (6%) achieved ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03499808

NCT03499808 | S1702 Isatuximab in Treating Patients ... 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.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118699215

A Phase II Study of Isatuximab (SAR650984) (NSC-795145 ... Conclusions: Isatuximab demonstrates encouraging efficacy in previously treated patients with AL amyloidosis. The administration of isatuximab ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/08/NCT03499808/Prot_SAP_002.pdf

a phase ii study of isatuximab (sar650984) (nsc-795145) for ... To evaluate efficacy of isatuximab in relapsed/ refractory immunoglobulin amyloid light chain (AL) amyloidosis as measured by organ specific response rates.

5. jons-online.com jons-online.com/multiple-myeloma/isatuximab-for-patients-with-previously-treated-al-amyloidosis-a-phase-2-study

Isatuximab for Patients with Previously Treated AL ... Overall hematologic response rate was 77%. Of the patients receiving ≥1 doses of isatuximab, hematologic complete response, very good partial response, and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04270409

Study Details | NCT04270409 | Isatuximab in Combination ... Primary Objectives: Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/892/530850/Efficacy-and-Safety-of-Isatuximab-Pomalidomide-and

Efficacy and Safety of Isatuximab, Pomalidomide and ... The ISAMYP study evaluates the efficacy and safety of the combination of isatuximab (anti-CD38 mAb), pomalidomide and dexamethasone (IsaPd), in ...

8. conference-correspondent.com conference-correspondent.com/highlights/ash/ash-2020-mm/503:a-phase-2-study-of-isatuximab-for-patients-with-previously-treated-al-amyloidosis

A Phase 2 Study of Isatuximab for Patients with Previously ... The use of isatuximab among these patients was associated with a good safety profile, which was similar to other CD38 monoclonal antibodies.