Trial Title:
Daratumumab Maintenance Therapy for Improving Survival in Patients With Light Chain Amyloidosis, EMILIA Trial
NCT ID:
NCT05898646
Condition:
AL Amyloidosis
Conditions: Official terms:
Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Daratumumab
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Intervention type:
Biological
Intervention name:
Daratumumab
Description:
Given SC
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Other name:
Daratumumab Biosimilar HLX15
Other name:
Darzalex
Other name:
HLX15
Other name:
HuMax-CD38
Other name:
JNJ-54767414
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo echocardiography
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Other name:
EC
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo x-ray imaging
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Plain film radiographs
Other name:
Radiographic Imaging
Other name:
Radiographic imaging procedure (procedure)
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (6 cycles of daratumumab)
Arm group label:
Arm II (18 cycles of daratumumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Summary:
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.
Detailed description:
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 bone marrow
biopsy and blood sample collection 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 bone marrow biopsy and
blood sample collection 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.
Criteria for 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 =< 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
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clincal Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Udit Yadav, M.B.B.S.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Taimur Sher, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Eli Muchtar, M.D.
Email:
Principal Investigator
Start date:
July 17, 2023
Completion date:
November 1, 2024
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05898646
https://www.mayo.edu/research/clinical-trials
