Daratumumab Maintenance Therapy for Improving Survival in Patients With Light Chain Amyloidosis, EMILIA Trial
AL Amyloidosis
About this trial
This is an interventional treatment trial for AL Amyloidosis
Eligibility Criteria
Inclusion Criteria: 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 daratumumab (Dara)-CyBorD-based induction treatment =< 84 days prior to registration 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) Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Provide written informed consent NOTE: Informed consent required =< 90 days prior registration Ability to complete questionnaire(s) by themselves or with assistance Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) Exclusion Criteria: 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 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 Known to have presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment or known or suspected active hepatitis C infection Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection Unstable angina pectoris Psychiatric illness/social situations that would limit compliance with study requirements
Sites / Locations
- Mayo Clinic in ArizonaRecruiting
- Mayo Clinic in Florida
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (6 cycles of daratumumab)
Arm II (18 cycles of daratumumab)
Patients receive daratumumab SC for up to 6 cycles on study. Patients also undergo x-ray imaging at screening and bone marrow biopsy at screening and on study. Patients with cardiac involvement also undergo echocardiography throughout the trial.
Patients receive daratumumab SC for up to 18 cycles on study. Patients also undergo x-ray imaging at screening and bone marrow biopsy at screening and on study. Patients with cardiac involvement also undergo echocardiography throughout the trial.