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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal duration of maintenance therapy with daratumumab for individuals with light chain (AL) amyloidosis. Daratumumab, a monoclonal antibody, aids the immune system in destroying cancer cells. The trial compares two groups: one receiving six cycles of treatment and another receiving 18 cycles. It targets those who have already undergone initial treatment with daratumumab for AL amyloidosis and completed six cycles of a specific induction therapy. Participants must have confirmed AL amyloidosis and require ongoing therapy for organ disease. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that daratumumab is generally safe for people. In a study with 683 patients, including 193 with light chain (AL) amyloidosis, participants tolerated daratumumab well. Most did not experience serious side effects.

Some had mild to moderate reactions, such as fatigue or cold symptoms, while serious side effects were rare. This suggests that daratumumab is likely safe for those considering joining a trial. However, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for amyloidosis?

Unlike the standard treatments for amyloidosis, which often involve chemotherapy or stem cell transplants, daratumumab is unique because it specifically targets CD38, a protein found on the surface of certain cells involved in this condition. Researchers are excited about this because daratumumab is administered subcutaneously, making it potentially more convenient and less invasive than traditional methods. Additionally, its targeted approach may lead to fewer side effects and improved outcomes for patients with amyloidosis, particularly those with cardiac involvement.

What evidence suggests that daratumumab maintenance therapy could be effective for AL amyloidosis?

Research has shown that daratumumab effectively treats conditions like AL amyloidosis. In one study, 70% of patients who took daratumumab with other medicines did not experience disease progression after 28 months. The ANDROMEDA study found that 53.3% of patients achieved a complete response with daratumumab, compared to 18.1% with other treatments. This indicates that daratumumab can significantly slow down the disease. It works by attaching to the CD38 protein, enabling the immune system to find and destroy cancer cells. In this trial, participants will receive daratumumab in one of two treatment arms: Arm I, with 6 cycles, or Arm II, with 18 cycles. These findings suggest that daratumumab could be highly beneficial for treating AL amyloidosis. ^{1 2 4 6 7}

Who Is on the Research Team?

Taxiarchis Kourelis, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 undergo bone marrow aspiration, blood sample collection, and optional bone marrow biopsy 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 undergo bone marrow aspiration, blood sample collection, and optional bone marrow biopsy 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

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Safety and Efficacy of Subcutaneous Daratumumab in ... At median follow-up of 7.5 months, progression of disease had been observed in 51% of patients in each arm. Median progression-free survival was ...

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DARZALEX FASPRO® (daratumumab and hyaluronidase ... New analysis from Phase 3 CEPHEUS study demonstrates 85 percent of patients who achieved MRD negativity (10-6) with DARZALEX FASPRO® were ...

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DARZALEX FASPRO - AMY3001 (ANDROMEDA) Study The primary endpoint of hematologic complete response (CR) was achieved in 53.3% of the D-VCd arm vs 18.1% of the VCd arm, respectively ( ...

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Darzalex | European Medicines Agency (EMA) After about 28 months, 70% (246 out of 350) of patients treated with Darzalex in combination with the other three medicines had no worsening of their disease ...

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Daratumumab (Darzalex) and Daratumumab and ... The median overall survival (OS) of MM patients has increased significantly with patients younger than 50 years of age experiencing a 10-year survival rate of ...

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DARZALEX® (daratumumab) & DARZALEX FASPRO ... Response data presented are cumulative deepest response rates achieved by 6, 9, and 18 months for patients who continued all trial treatment for at least 18 ...

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Darzalex Faspro - accessdata.fda.gov In a pooled safety population of 683 patients with multiple myeloma (N=490) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy ...