Daratumumab Maintenance Therapy for Improving Survival in Patients With Light Chain Amyloidosis, EMILIA Trial

AL Amyloidosis Clinical Trial

Official title: Phase II Study Evaluating Maintenance in Light Chain Amyloidosis (EMILIA)

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the event-free survival (EFS) after 3-6 versus 18 cycles of daratumumab maintenance following 6 cycles induction of daratumumab-cyclophosphamide-bortezomib-dexamethasone (CyBorD) in newly diagnosed AL amyloidosis.

SECONDARY OBJECTIVES:

I. To determine the rate of hematological response at end of maintenance in each arm.

II. To assess minimal residual disease rates by next generation multiparametric flow cytometry at study registration and at the end maintenance.

III. To determine organ response rate at 6, 12, 18, 24 and 36 months from registration in each arm (organ response will be assessed based on organ-related values at diagnosis).

IV. To determine time to next therapy (TTNT) after 3-6 versus 18 cycles daratumumab maintenance.

V. To determine time to organ response in those who did not achieve organ response at trial registration.

VI. To determine time to deep organ response based on revised organ response criteria for heart and kidneys.

VII. To determine time to organ progression, defined as the time between registration to date of organ progression per organ progression criteria.

VIII. To determine rate of pneumonia, sepsis and/or upper respiratory infections and any grade >= 3 infection in both arms within 3 years from registration.

IX. To determine overall survival after 3-6 versus 18 cycles daratumumab maintenance.

CORRELATIVE RESEARCH OBJECTIVE:

I. To assess overall health-related quality of life, as measured by Patient Reported Outcomes Measurement Information System (PROMIS)-29 health questionnaire and selected items for the Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) questionnaire at registration, and at 3, 6, 12, 18 and 36 months from registration.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: 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.

ARM II: 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.

After completion of study treatment, patients are followed up every 3 months for up to 36 months from registration, and then up to 5 years from starting the study for survival status. ;

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis

• NCT number: NCT05898646
• Study type: Interventional
• Source: Mayo Clinic
• Contact: Clinical Trials Referral Office
• Phone: 855-776-0015
• Email: mayocliniccancerstudies@mayo.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: July 17, 2023
• Completion date: November 1, 2024