Daratumumab Maintenance Therapy for Amyloidosis

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Daratumumab

Disqualifiers: Pregnancy, Multiple myeloma, Hepatitis B, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 16

96 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the drug Daratumumab for Amyloidosis?

Research shows that Daratumumab, when used with other medications, significantly improves blood and organ responses in patients with AL amyloidosis, a condition where abnormal proteins build up in organs. It has been effective in both newly diagnosed and previously treated patients, showing good results in improving heart and kidney function. ^{1 2 3 4 5}

Is daratumumab safe for use in humans?

Daratumumab has been shown to be generally safe in humans, with studies reporting an acceptable safety profile. Common side effects include respiratory infections and atrial fibrillation (irregular heartbeat), but serious infusion-related reactions were not observed. ^{1 4 5 6 7}

How does the drug daratumumab differ from other treatments for amyloidosis?

Daratumumab is unique because it is a monoclonal antibody that specifically targets CD38 on plasma cells, which are responsible for producing the harmful proteins in amyloidosis. Unlike traditional treatments, daratumumab is used in combination with other drugs and has shown to significantly improve response rates and organ function in patients with amyloidosis. ^{1 4 5 7 8}

What is the purpose of this trial?

This phase II trial compares shorter-duration versus longer-duration maintenance therapy with daratumumab for improving survival in patients who have received initial treatment with daratumumab for light chain (AL) amyloidosis. Maintenance therapy is treatment that is given to help keep cancer from coming back after it has disappeared following initial therapy. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Daratumumab is commonly prescribed as initial treatment for patients with AL amyloidosis. However, it is not known what role daratumumab may play in the maintenance therapy period of patients with AL amyloidosis. This phase II trial compares shorter duration maintenance to longer duration maintenance for improving survival in patients with AL amyloidosis.

Research Team

Eli Muchtar, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with newly diagnosed AL amyloidosis who've completed specific induction therapy and achieved a certain response level. They must have good enough health to perform daily activities, be able to complete questionnaires, and agree to follow-up visits. Pregnant or nursing individuals, those with hepatitis B/C or HIV on treatment, and patients with multiple myeloma are excluded.

Inclusion Criteria

Your blood platelet count is at least 50,000 per cubic millimeter.

Your body has enough infection-fighting white blood cells.

I finished my daratumumab-based treatment less than 84 days ago.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am of childbearing age and not using birth control.

I am immunocompromised or HIV positive and on antiretroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Treatment

Participants receive 6 cycles of daratumumab-cyclophosphamide-bortezomib-dexamethasone (CyBorD) as initial treatment

24 weeks

6 visits (in-person)

Maintenance Treatment

Participants receive daratumumab maintenance therapy, with cycles repeating every 28 days for up to 6 or 18 cycles depending on the arm

24-72 weeks

6-18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

36 months

Every 3 months

Treatment Details

Interventions

• Daratumumab

Trial Overview The EMILIA Trial is testing whether daratumumab maintenance therapy can extend the time without disease symptoms after initial treatment in AL amyloidosis patients. It compares the effects of continuing daratumumab for 3-6 cycles versus 18 cycles following an induction phase.

Participant Groups

Group I: Arm I (6 cycles of daratumumab) Experimental Treatment 6 Interventions

Patients receive daratumumab subcutaneously (SC) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles on study. Patients also undergo x-ray imaging at screening and optional bone marrow biopsy and blood sample collection throughout the study. Patients with cardiac involvement also undergo echocardiography throughout the trial.

Group II: Arm II (18 cycles of daratumumab) Active Control 6 Interventions

Patients receive daratumumab SC on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 18 cycles on study. Patients also undergo x-ray imaging at screening and optional bone marrow biopsy and blood sample collection throughout the study. Patients with cardiac involvement also undergo echocardiography throughout the trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

Daratumumab, a monoclonal antibody targeting CD38, shows promising results in treating AL amyloidosis, with early phase I and II studies indicating it is well-tolerated and induces rapid, deep responses in patients.

As autologous stem cell transplantation is not an option for most patients at diagnosis, daratumumab may become a crucial part of AL amyloidosis treatment, especially as phase III trials are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the treatment of AL amyloidosis. Sidiqi, MH., Gertz, MA.[2023]

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]

In the phase III ANDROMEDA trial, subcutaneous daratumumab combined with bortezomib, cyclophosphamide, and dexamethasone significantly improved the rate of complete hematological response in patients with newly diagnosed systemic AL amyloidosis compared to the standard treatment alone.

This combination therapy not only produced rapid and deep responses but also resulted in better progression-free survival and higher rates of cardiac and renal responses at 6 and 12 months, while maintaining an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis. Blair, HA.[2022]

In a study of 72 previously treated patients with multiple myeloma and AL amyloidosis, daratumumab showed a high efficacy, with 82% of patients achieving a hematologic response after eight infusions, including 16% complete responses and 42% very good partial responses.

Daratumumab also demonstrated notable renal responses in 60% of patients and cardiac responses in 29%, indicating its potential as an effective treatment option for patients with relapsed/refractory AL amyloidosis, especially those with high plasma cell burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate. Milani, P., Fazio, F., Basset, M., et al.[2020]

Daratumumab, administered to 22 patients with relapsed AL amyloidosis, demonstrated a high efficacy with 86% achieving hematologic complete or very-good-partial responses, indicating its potential as a strong treatment option.

The treatment was well tolerated, with no severe infusion-related reactions and manageable adverse events, such as respiratory infections and atrial fibrillation, suggesting a favorable safety profile for daratumumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Sanchorawala, V., Sarosiek, S., Schulman, A., et al.[2021]

The population pharmacokinetics (popPK) analysis of subcutaneous daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone showed that the 1800-mg flat dose is effective for treating newly diagnosed systemic amyloid light-chain amyloidosis, based on data from 183 patients in the ANDROMEDA study.

There was no significant relationship found between daratumumab systemic exposure and safety or efficacy outcomes, indicating that the selected dose does not require adjustments based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light-Chain Amyloidosis. Luo, MM., Zhu, PP., Nnane, I., et al.[2022]

The addition of daratumumab, an anti-CD38 monoclonal antibody, to the standard treatment regimen of cyclophosphamide-bortezomib-dexamethasone (CyBorD) significantly improves hematologic complete response rates and organ responses in previously untreated patients with primary systemic AL amyloidosis, as shown in the large phase-III ANDROMEDA study.

Daratumumab has a favorable toxicity profile and demonstrates rapid and deep responses in patients with relapsed or refractory AL amyloidosis, making it a promising treatment option and leading to its approval as the first therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis. Theodorakakou, F., Dimopoulos, MA., Kastritis, E.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Daratumumab for the treatment of AL amyloidosis. [2023]

3. 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]

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

Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis. [2022]

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

High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate. [2020]

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

Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light-Chain Amyloidosis. [2022]

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

Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis. [2021]