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

NCT05898646 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: MC220802R21CA28889822-011048
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Event free survival

  The point estimate for the hazard ratio and corresponding one-sided 85% confidence interval will be generated with a stratified Cox regression (using the trial stratification factors) that has treatment arm as an exploratory variable.

  From registration up to 36 months

Secondary Outcomes (4)

• Hematological response

  At the end of maintenance treatment

• Minimal residual disease (MRD) negativity rate

  Up to 36 months

• Organ response rates

  At 6, 12, 18, 24, and 36 months from registration

• Overall survival (OS)

  Time from registration to death from any cause, assessed up to 5 years

Study Arms (2)

Arm I (6 cycles of daratumumab)

EXPERIMENTAL

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.

Procedure: Bone Marrow Aspiration; Biological: Daratumumab; Procedure: Echocardiography Test; Other: Questionnaire Administration; Procedure: X-Ray Imaging; Procedure: Biospecimen Collection

Arm II (18 cycles of daratumumab)

ACTIVE COMPARATOR

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.

Procedure: Bone Marrow Aspiration; Biological: Daratumumab; Procedure: Echocardiography Test; Other: Questionnaire Administration; Procedure: X-Ray Imaging; Procedure: Biospecimen Collection

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

Daratumumab BIOLOGICAL

Given SC

Also known as: Daratumumab Biosimilar HLX15, Darzalex, HLX15, HuMax-CD38, JNJ-54767414

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

Questionnaire Administration OTHER

Ancillary studies

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (6 cycles of daratumumab); Arm II (18 cycles of daratumumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Histological confirmation of AL amyloidosis with adequate typing (mass spectrometry, immunohistochemistry, immunofluorescence, immunogold)
• AL amyloidosis with organ disease requiring therapy
• NOTE: Disease requiring therapy is referred to the time of diagnosis. There are no limitations in baseline measurable disease parameters
• Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum MASS-FIX) obtained at time of diagnosis before induction therapy initiated and available for review to be enrolled.
• NOTE: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained
• Patients must have completed 6 cycles of daratumumab (Dara)-CyBorD-based induction treatment prior to registration or have a plan to complete cycle 6 prior to cycle 1 day 1. NOTE: treatment in the study is allowed only after the completion of 6 cycles of induction
• Patients must have achieved a hematological complete response (CR) (irrespective of organ response achievement) or hematological very good partial response (VGPR) (irrespective of organ response achievement) or hematological low-difference in involved and uninvolved free light chain (dFLC) partial response (PR) (irrespective of organ response achievement) or hematological PR with at least one organ response after receiving Dara-CyBorD-based induction.
• NOTE: Patients with baseline dFLC \< 5 mg/dL, must have achieved hematological CR, or dFLC \< 1 mg/dL or achieved organ response prior to randomization
• Patients in whom bortezomib and/or cyclophosphamide were omitted from induction due to toxicity concerns or adverse effects are allowed. Patients must receive at least daratumumab and dexamethasone at induction to qualify for the study
• NOTE: Dexamethasone use does not need to be carried to end of induction for eligibility consideration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
• Hemoglobin \>= 8.0 g/dL (obtained =\< 28 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 28 days prior to registration)
• Platelet count \>= 50,000/mm\^3 (obtained =\< 28 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an agent that has possible genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
• Received \>1 cycle of daratumumab maintenance after end of induction therapy and prior to registration
• Multiple myeloma at time of diagnosis as defined by any of the following:
• Hypercalcemia: Serum calcium \> 1 mg/dL higher than upper limit of normal or \> 11 mg/dL
• Renal insufficiency: Creatinine clearance \< 40 mL per min or serum creatinine \> 2 mg/dL attributed to high circulating light chains (i.e. cast nephropathy) or hypercalcemia
• Anemia: Hemoglobin \> 2 g/dL below lower limit of normal, or \< 10 g/dL, attributed to high marrow myeloma infiltration
• Bone lesions: \>= 1 osteolytic lesion on skeletal x-ray, computed tomography (CT), or positron emission tomography (PET)-CT (bone imaging is not mandatory but based on clinical suspicion)
• Clonal bone marrow plasma cells \>= 60%
• \> 1 focal lesion on magnetic resonance imaging (MRI) (MRI is not mandatory but based on clinical suspicion)
• If bone imaging (CT, MRI, PET-CT) was not done at time of diagnosis it is not needed to be performed at registration to rule out bone disease
• \>= 40% BMPCs irrespective of the above
• The study will allow patients with involved: uninvolved serum-free light chain (sFLC) ratio \>= 100 if this is the only criteria that defines amyloidosis if all the above criteria are not met

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; X-Rays; Phantoms, Imaging; Specimen Handling

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Taxiarchis Kourelis, MD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: June 12, 2023
• Study Start: July 17, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (2)