RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-07-17

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05898646

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 =\< 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)	* 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

Inclusion Criteria

Exclusion 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 =\< 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)

* 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

Contacts and Locations

Study Contact

Clinical Trials Referral Office

CONTACT

855-776-0015

mayocliniccancerstudies@mayo.edu

Principal Investigator

Eli Muchtar, M.D.

PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Study Locations (Sites)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259

United States

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

United States

Collaborators and Investigators

Sponsor: Mayo Clinic

Eli Muchtar, M.D., PRINCIPAL_INVESTIGATOR, Mayo Clinic in Rochester

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-17

Study Completion Date2026-12

Study Record Updates

Study Start Date2023-07-17

Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

AL Amyloidosis