ClinicalTrials.gov record NCT05898646
Daratumumab Maintenance Therapy for Improving Survival in Patients With Light Chain Amyloidosis, EMILIA Trial
Phase II Study Evaluating Maintenance in Light Chain Amyloidosis (EMILIA)
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This randomized phase II trial compares shorter (3–6 cycles) versus longer (18 cycles) daratumumab maintenance given every 28 days after six cycles of daratumumab‑CyBorD induction in adults with AL (light‑chain) amyloidosis who have achieved a qualifying hematologic response. Participants receive subcutaneous daratumumab, undergo blood tests and biospecimen collection, bone marrow aspiration, x‑rays, questionnaires, and heart imaging if they have cardiac involvement, then regular follow‑up for several years. The study measures event‑free survival, hematologic and organ responses, infections, time to next therapy, minimal residual disease, and overall survival.
What it is studying. Whether different lengths of daratumumab maintenance (shorter vs longer) affect event‑free survival, hematologic and organ responses, MRD rates, infection rates, time to next therapy, and overall survival.
What the researchers hope to learn. Primary goal: compare event‑free survival after 3–6 versus 18 cycles of daratumumab maintenance following 6 cycles of daratumumab‑CyBorD induction. Secondary goals: measure hematologic response rates at end of maintenance; assess minimal residual disease (MRD) negativity; evaluate cardiac, renal, and hepatic organ response rates at multiple time points; determine time to next therapy, time to organ response and deep organ response, time to organ progression; record rates of pneumonia, sepsis, upper respiratory infections and grade ≥3 infections within 3 years; estimate overall survival. Correlative objective: assess health‑related quality of life using PROMIS‑29 and selected PRO‑CTCAE items at defined intervals.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Biological
- Daratumumab
- Procedure
- Bone Marrow Aspiration
- Echocardiography Test
- X-Ray Imaging
- Biospecimen Collection
- Other
- Questionnaire Administration
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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 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)
- 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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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 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. 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 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. 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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After completing six cycles of daratumumab‑CyBorD induction, participants are randomized to receive subcutaneous daratumumab on day 1 of each 28‑day cycle for either up to 6 cycles or up to 18 cycles. Study procedures include bone marrow aspiration (with an optional bone marrow biopsy), regular blood sample collection, x‑ray imaging at screening, and echocardiography for those with heart involvement. Participants complete quality‑of‑life and symptom questionnaires at registration and at 3, 6, 12, 18 and 36 months. After treatment, participants are followed every 3 months for up to 36 months and have survival status checked up to 5 years from study start.
How the study is structured. Randomized, open‑label phase II trial with two parallel groups. Adults are assigned to receive daratumumab subcutaneously every 28 days for either up to 6 cycles (shorter maintenance) or up to 18 cycles (longer maintenance). Patients have scheduled blood tests and biospecimen collection, bone marrow aspiration, x‑ray imaging at screening, questionnaires, and echocardiography if they have heart involvement. After treatment, participants are followed every 3 months up to 36 months and then for survival up to 5 years.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on AL amyloidosis
Important dates
- Study start
- Sep 6, 2023
- Primary completion
- Nov 30, 2029 (estimated)
- Study completion
- Nov 30, 2031 (estimated)
- Target enrollment
- 96 participants (estimated)
- Last updated on registry
- Oct 1, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Mayo Clinic
- Collaborators
- National Cancer Institute (NCI)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Clinical Trials Referral Office 📞 855-776-0015 ✉ mayocliniccancerstudies@mayo.edu
Participating sites (2)
- Mayo Clinic in ArizonaRecruiting
Scottsdale, Arizona, 85259 · United States
- Clincal Trials Referral Office · 855-776-0015 · mayocliniccancerstudies@mayo.edu
- Udit Yadav, MBBS
- Mayo Clinic in RochesterRecruiting
Rochester, Minnesota, 55905 · United States
- Clinical Trials Referral Office · 855-776-0015 · mayocliniccancerstudies@mayo.edu
- Taxiarchis Kourelis, MD
Terms used on this page · explanations by MedicalUpdates.ai
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- serum free light chain
- Small pieces of antibody protein made by plasma cells and measured in a blood test. In some conditions, such as AL amyloidosis, abnormal free light chains are the source of the disease.
- complete response
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- very good partial response
- A response category used in some blood conditions meaning the disease marker has fallen a great deal but not disappeared. The exact definition depends on the condition and the study.
- dFLC
- The difference between the abnormal ('involved') and normal ('uninvolved') free light chain levels in the blood. Used in some conditions to decide whether disease is measurable and to track response.
- randomization
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- computed tomography
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
- positron emission tomography
- A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
- magnetic resonance imaging
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- PRIMARY OBJECTIVE
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- minimal residual disease
- Very small amounts of disease that remain after treatment and can only be found with highly sensitive tests. 'MRD-negative' means none was detected at the test's limit. The exact test and threshold depend on the condition and the study.
- overall survival
- The length of time from the start of the study or treatment that participants are alive, whatever the cause of death.
- Adverse Events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- echocardiography
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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