Daratumumab Maintenance Therapy for Amyloidosis
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Mayo Clinic
Must be taking: Daratumumab
Disqualifiers: Pregnancy, Multiple myeloma, Hepatitis B, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
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.
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.
12345Is 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.
14567How 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.
14578Eligibility 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.
+12 more
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.
+4 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (6 cycles of daratumumab)Experimental Treatment6 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 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 Control6 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 bone marrow biopsy and blood sample collection throughout the study. Patients with cardiac involvement also undergo echocardiography throughout the trial.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in ArizonaScottsdale, AZ
Mayo Clinic in FloridaJacksonville, FL
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
References
Daratumumab in AL Amyloidosis: A Real-Life Experience of the "RTM" (Regional Tuscan Myeloma Network). [2022]Systemic amyloidosis arises from monoclonal CD38+ plasma cells that produce misfolded immunoglobulin light chains, which form amyloid fibrils that are deposited into different tissues, leading to organ damage. Daratumumab is a human IgG/k monoclonal antibody that targets CD38, a glycoprotein uniformly expressed on human plasma cells. Daratumumab has been utilized in recent years with unprecedented responses in multiple myeloma. In patients with relapsed or refractory AL amyloidosis, daratumumab has shown promising efficacy in terms of hematologic responses and improvement in organ function. Here, we report real-life treatment with Daratumumab in 33 AL amyloidosis patients treated within the Regional Tuscan Myeloma network at 5 centers with associated MGUS or SMM (n = 15) or symptomatic MM (n = 18). Patients were treated at relapsed/refractory disease stages (n = 29) with a median of one previous line of therapy or at diagnosis (n = 4). Daratumumab showed good efficacy, representing 60% of good hematological responses and 50% of organ responses in a real-life population of patients with an acceptable toxicity profile.
Daratumumab for the treatment of AL amyloidosis. [2023]Autologous stem cell transplantation (ASCT) has been used as treatment for immunoglobulin light-chain (AL) amyloidosis for over two decades with improving outcomes; however, the majority of patients are not candidates for this therapy at diagnosis. Novel agents such as immunomodulatory drugs, proteasome inhibitors, and immunotherapy with monoclonal antibodies targeting CD38 have been adopted from the multiple myeloma spheres with encouraging results. Herein, we discuss the role of daratumumab, a monoclonal antibody to CD38, in the treatment of AL amyloidosis. We focus on its mechanism of action, tolerability, and the current published data on its use in AL amyloidosis. Early data from phase I and phase II studies show that daratumumab is tolerated well in this population and induces rapid and deep responses. Phase III trials are currently accruing and we envision daratumumab becoming a key component in the treatment of AL amyloidosis in the future.
Daratumumab for relapsed AL amyloidosis-When cumulative real-world data precedes clinical trials: A multisite study and systematic literature review. [2021]Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.
Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis. [2022]Subcutaneous daratumumab (DARZALEX®) co-formulated with recombinant human hyaluronidase (DARZALEX FASPRO®) is approved in several countries, including the USA and those of the EU, for use in combination with bortezomib, cyclophosphamide and dexamethasone for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis. Daratumumab is a CD38-targeting, human IgG1κ monoclonal antibody. In the pivotal phase III ANDROMEDA trial in adults with newly diagnosed systemic AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide and dexamethasone significantly increased the proportion of patients achieving a haematological complete response relative to bortezomib, cyclophosphamide and dexamethasone alone (primary endpoint). Daratumumab combination therapy produced rapid and deep haematological responses which were associated with improved major organ deterioration progression-free survival (PFS). The addition of daratumumab also led to higher cardiac and renal response rates at 6 and 12 months. Daratumumab had an acceptable tolerability profile when used as combination therapy. Therefore, daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone represents an important emerging first-line treatment option for patients with systemic AL amyloidosis.
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]Daratumumab demonstrated activity in the treatment of AL amyloidosis in two recently concluded phase II clinical trials in relapsed and refractory patients. Its role in upfront therapy is under evaluation in a phase III study. In this report we evaluated the safety and efficacy of 28-day cycles of daratumumab (single agent or combined with bortezomib or lenalidomide) in 72 previously treated patients with multiple myeloma and AL amyloidosis. Fifty (69%) were refractory to the last line of therapy. After eight infusions of daratumumab, 59 patients (82%) achieved a hematologic response, with 12 (16%) complete responses (CRs) and 30 (42%) very good partial responses (VGPRs). After 16 infusions, the quality of response improved with 22 patients (30%) achieving CR and 21 (29%) attaining VGPR. Cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). Daratumumab is highly effective in heavily pretreated patients with relapsed/refractory AL amyloidosis and high bone marrow plasma cell burden. Renal responses, which are usually rare in this setting, were frequently observed.
Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. [2021]Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.
Population Pharmacokinetics and Exposure-Response Modeling of Daratumumab Subcutaneous Administration in Patients With Light-Chain Amyloidosis. [2022]The purpose of this study is to characterize the population pharmacokinetics (popPK) of subcutaneous (SC) daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone and explore the relationship between daratumumab systemic exposure and selected efficacy and safety end points in patients with newly diagnosed systemic amyloid light-chain amyloidosis. The popPK analysis included pharmacokinetic and immunogenicity data from patients receiving daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone in the ANDROMEDA study (AMY3001; safety run-in, n = 28; randomized phase, n = 183). Nonlinear mixed-effects modeling was used to characterize the popPK and quantify the impact of potential covariates. The exposure-response (E-R) analysis included data from all patients in the randomized phase of ANDROMEDA (n = 388). Logistic regression and survival analysis were used to evaluate the relationships between daratumumab systemic exposure and efficacy end points. The E-R analysis on safety was conducted using quartile comparison and logistic regression analysis. The observed concentration-time data of daratumumab SC were well described by a 1-compartment popPK model with first-order absorption and parallel linear and nonlinear Michaelis-Menten elimination pathways. None of the investigated covariates were determined to be clinically meaningful. Daratumumab systemic exposure was generally similar across subgroups that achieved different levels of hematologic response, and there was no apparent relationship between daratumumab systemic exposure and the investigated safety end points. In conclusion, the popPK and E-R analyses supported the selected 1800-mg flat dose of daratumumab SC in combination with the bortezomib, cyclophosphamide, and dexamethasone regimen for the treatment of light-chain amyloidosis. No dose adjustment was recommended for investigated covariates.
Daratumumab plus CyBorD for patients with newly diagnosed light chain (AL) amyloidosis. [2021]Primary systemic immunoglobulin light chain (AL) amyloidosis is caused by a plasma cell clone of, usually low, malignant potential that expresses CD38 molecules on their surface. Treatment of AL amyloidosis is based on the elimination of the plasma cell clone. The combination of cyclophosphamide-bortezomib-dexamethasone (CyBorD) is the most widely used and is considered a standard of care; however, complete hematologic response rates and organ response rates remain unsatisfactory. Daratumumab, an anti-CD38 monoclonal antibody, has demonstrated encouraging results, with rapid and deep responses, in patients with relapsed or refractory AL amyloidosis as monotherapy with a favorable toxicity profile. The large phase-III, randomized, ANDROMEDA study evaluated the addition of daratumumab to CyBorD in previously untreated patients with AL amyloidosis and demonstrated that addition of daratumumab can substantially improve hematologic complete response rates, survival free from major organ deterioration or hematologic progression, and organ responses. In this review, we discuss the role of daratumumab in the treatment of AL amyloidosis, its mechanism of action, and the results of ANDROMEDA study that led to the first approved therapy for AL amyloidosis.