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

Launched by MAYO CLINIC · Jun 2, 2023

Keywords

ClinConnect Summary

The EMILIA Trial is studying how different lengths of maintenance therapy with a medication called daratumumab can help patients with AL amyloidosis live longer after their initial treatment. Maintenance therapy is like a follow-up treatment that aims to keep the disease from coming back once it has improved. Daratumumab is a type of medicine called a monoclonal antibody that helps the immune system fight cancer cells. In this trial, researchers are comparing shorter and longer durations of daratumumab treatment to see which is more effective for improving survival.

To participate in this trial, patients need to be at least 18 years old and have been diagnosed with AL amyloidosis that requires treatment. They should have completed a specific initial treatment with daratumumab and have shown a good response to it. Participants will be monitored throughout the study and may need to return for follow-up visits. It’s important to note that the trial is currently recruiting participants, so those who meet the eligibility criteria can join. If you're considering participating, make sure to discuss it with your doctor to understand how it might benefit you.

Gender

ALL

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 6 cycles of daratumumab (Dara)-CyBorD-based induction treatment prior to registration or have a plan to complete cycle 6 prior to registration. 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)
• • 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
• • 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
• • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Note: Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• • 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