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

Primary Purpose

AL Amyloidosis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bone Marrow Biopsy
Daratumumab
Echocardiography
Questionnaire Administration
X-Ray Imaging
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AL Amyloidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (6 cycles of daratumumab)

Arm II (18 cycles of daratumumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Hematological response
A success is defined as a complete response (CR), very good partial response (VGPR) and partial response (PR). Hematological response must be maintained or improved during maintenance. Loss of level of hematological response (i.e., CR to VGPR/PR/progressive disease [PD], VGPR to PR/PD or PR to PD) will be considered a failure. The rate of hematological response will be defined as the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. All responses will be assessed and compared to values at diagnosis (and not at trial registration).
Minimal residual disease (MRD) negativity rate
Will be estimated by the number of successes divided by the total number of evaluable patients who consented for MRD assessment. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
Organ response rates
Cardiac, renal, and hepatic response rates will be evaluated separately. The rate of organ response will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. All responses will be assessed and compared to values at diagnosis (and not at trial registration)
Overall survival (OS)
Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by arm (6 vs. 18 cycles of daratumumab maintenance).

Full Information

First Posted
June 2, 2023
Last Updated
September 26, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT05898646
Brief Title
Daratumumab Maintenance Therapy for Improving Survival in Patients With Light Chain Amyloidosis, EMILIA Trial
Official Title
Phase II Study Evaluating Maintenance in Light Chain Amyloidosis (EMILIA)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 17, 2023 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the event-free survival (EFS) after 3-6 versus 18 cycles of daratumumab maintenance following 6 cycles induction of daratumumab-CyBorD in newly diagnosed AL amyloidosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AL Amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (6 cycles of daratumumab)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (18 cycles of daratumumab)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Biopsy
Other Intervention Name(s)
Biopsy of Bone Marrow, Biopsy, Bone Marrow
Intervention Description
Undergo bone marrow biopsy
Intervention Type
Biological
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Intervention Description
Given SC
Intervention Type
Procedure
Intervention Name(s)
Echocardiography
Other Intervention Name(s)
EC
Intervention Description
Undergo echocardiography
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Procedure
Intervention Name(s)
X-Ray Imaging
Other Intervention Name(s)
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
Intervention Description
Undergo x-ray imaging
Primary Outcome Measure Information:
Title
Event free survival
Description
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.
Time Frame
From registration up to 36 months
Secondary Outcome Measure Information:
Title
Hematological response
Description
A success is defined as a complete response (CR), very good partial response (VGPR) and partial response (PR). Hematological response must be maintained or improved during maintenance. Loss of level of hematological response (i.e., CR to VGPR/PR/progressive disease [PD], VGPR to PR/PD or PR to PD) will be considered a failure. The rate of hematological response will be defined as the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. All responses will be assessed and compared to values at diagnosis (and not at trial registration).
Time Frame
At the end of maintenance treatment
Title
Minimal residual disease (MRD) negativity rate
Description
Will be estimated by the number of successes divided by the total number of evaluable patients who consented for MRD assessment. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
Time Frame
Up to 36 months
Title
Organ response rates
Description
Cardiac, renal, and hepatic response rates will be evaluated separately. The rate of organ response will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. All responses will be assessed and compared to values at diagnosis (and not at trial registration)
Time Frame
At 6, 12, 18, 24, and 36 months from registration
Title
Overall survival (OS)
Description
Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by arm (6 vs. 18 cycles of daratumumab maintenance).
Time Frame
Time from registration to death from any cause, assessed up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eli Muchtar, M.D.
Organizational Affiliation
Mayo Clinic in Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clincal Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Rafael Fonseca, M.D.
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Taimur Sher, M.D.
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Eli Muchtar, M.D.

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

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