This research study is for people who have newly diagnosed with AL (light chain) amyloidosis and have not yet received any treatment for this condition. The purpose of this study is to evaluate whether elranatamab, a type of immunotherapy drug, can produce deep remissions and organ recovery in people with newly diagnosed AL amyloidosis, and to compare two different dosing schedules. Elranatamab (brand name ELREXFIO™) is an investigational (experimental) drug in the setting of AL amyloidosis. It works by connecting immune cells (T-cells) directly to the abnormal plasma cells that are causing amyloidosis, triggering the immune system to destroy those cells. It is not approved by the Food and Drug Administration (FDA) for use in AL amyloidosis. Participants in this study will receive elranatamab as a series of injections under the skin (subcutaneously) over 6 treatment cycles (approximately 6 months). Treatment begins with inpatient "step-up" doses designed to reduce side effects, followed by either every-2-week or every-4-week dosing based on which study arm participants are randomly assigned to. Participants will have regular blood tests, physical exams, bone marrow biopsies, and heart assessments throughout the study, and follow-up visits for up to 2 years after treatment ends. This study is randomized, meaning that participants will be assigned by chance (similar to a coin flip) to one of two treatment arms. Participants cannot choose their arm. Participation in this research will last approximately 6 months of active treatment, followed by follow-up visits for up to 2 years (with an option to extend to 5 years).
Immunoglobulin light chain (AL) amyloidosis is a disorder of a certain type of blood cell (plasma cells). With this disorder, some plasma cells make abnormal, misfolded light chain proteins that can build up in tissues and organs, damaging them over time. In the United States, about 5 in every 100,000 people have this disorder. Even though it is rare, it can be very serious. Many people who have this disease are very sick upon diagnosis and require care from many different types of doctors. Cardiac (heart) involvement is the most common reason why people may get very sick and die. Contemporary plasma cell directed therapy has helped to improve outcomes, but many people still do not respond quickly or strongly enough. Some people still have worsening organ damage or cannot handle the strong treatments due to organ damage. In fact, early mortality is common, especially in people with cardiac involvement. There is a need for treatments that can quickly and safely lower harmful light chain levels, especially for people whose organs are already affected by the disease. Elranatamab is a type of drug called a bispecific antibody that connects a B cell maturation antigen (BCMA), a protein on plasma cells, with CD3, a protein on T cells. It can redirect T cells to kill plasma cells that are expressing BCMA. Treatments that use elranatamab have led to positive responses in people with multiple myeloma, a type of blood disease. There is early evidence to show that this drug may also help people with AL amyloidosis. This study will test elranatamab given for a set period of time in people with newly diagnosed AL amyloidosis. It will use two dosing schedules designed to balance efficacy with infection and tolerability risk in a population that is medically fragile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
All Participants will receive standard step-up dosing (SUD) of BCMA bispecific (elranatamab) in Cycle 1. They will receive 12 milligrams (mg) on Day 1, 32 mg on Day 3, 76 mg on Day 6, and one additional full dose (76 mg) on Day 13. They will then have 5 additional 28-day cycles, for a total duration of 6 months. For the 5 additional cycles, participants in Arm A will receive 76 mg of elranatamab every 2 weeks (q2). For the 5 additional cycles, participants in Arm B will receive 76 mg of elranatamab every 4 weeks (q4). The maximum duration of treatment for all participants is a total of 6 cycles (each 28 days in length), up to about 6 months.
Mayo Clinic
Rochester, Minnesota, United States
Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, United States
Efficacy of BCMA bispecific in treating newly diagnosed AL Amyloid, as measured by hematologic complete response (hCR) rates
hCR rate is defined as the proportion of participants who experience a normalization of free light chain (FLC) levels with negative serume and urine immunofixation, measured through blood tests, at the end of therapy.
Time frame: At end of therapy (after 6 cycles, up to 6 months)
Time to complete hematologic response (hCR)
Time to complete hCR is defined as the length of time from the start of treatment to time of complete hCR.
Time frame: Up to 6 months
Overall Response rate (ORR)
ORR is defined as the percentage of participants in Arm A vs Arm B who show a partial, very good partial or complete, hematological response from start of treatment to the end of treatment.
Time frame: At end of therapy (after 6 cycles, up to 6 months)
Duration of hematologic response
Duration of hematologic response is defined as the length of time in Arm A vs Arm B from first hematologic response until the disease progresses or the participant dies, whichever comes first.
Time frame: Up to 6 months
Progression free survival (PFS) rate
PFS rate is defined as the length of time from start of treatment until the disease progresses, the participant dies, or the trial ends, in Arm A vs Arm B.
Time frame: Up to 60 months
Overall survival
Overall survival is defined as the length of time from start of treatment until death, in Arm A vs Arm B.
Time frame: Up to 60 months
Percentage of participants who achieve organ response
Percentage of participants in Arm A vs Arm B who achieve organ (i.e., renal and cardiac) response.
Time frame: Up to 60 months
Time between the first treatment and first recorded involved organ response
Length of time between the first treatment and the best recorded involved organ response in Arm A vs Arm B.
Time frame: Up to 60 months
Major organ deterioration progression free survival (MOD-PFS)
MOD-PFS is defined as the length of time from start of treatment until organ deterioration response (heart, kidney, liver, and peripheral nervous system), the participant dies, the trial ends, or cessation of study drug due to a cause other than documented progression.
Time frame: Up to 60 months
Hospitalization rate
Hospitalization rate is defined as the percentage of subjects in Arm A vs Arm B that are hospitalized over time from the start of treatment to the end of the observed study follow up period.
Time frame: Up to 60 months
Rates of disease
Rates of disease is defined as the percentage of subjects in Arm A vs Arm B that experience a cardiac event or an infection from the start of treatment to observed study follow up period.
Time frame: Up to 60 months
Minimal Residual Disease (MRD) negativity rates at end of therapy
MRD negativity rates are measured from MRD test results of bone marrow aspirate samples using next generation flow cytometry with 10\^-5 sensitivity.
Time frame: At end of therapy (after 6 cycles, up to 6 months)
Minimal Residual Disease (MRD) negativity rates at 24 months
MRD negativity rates are measured from MRD test results of bone marrow aspirate samples using next generation flow cytometry with 10\^-5 sensitivity.
Time frame: At 24 months
Change in Quality of life (QoL)
QoL is measured using the Short Form 36 Questionnaire (SF-36) score. The questionnaire has 19 questions assessing frequency and severity of symptoms impacting quality of life that are answered on a 5-point Likert scale from Excellent/All of the time (4) to Very Severe/None of the time (0). Seven questions assess behaviors impacting quality of life answered Yes or No. Answers are scored, and higher scores indicate greater quality of life.
Time frame: Baseline, end of treatment (up to 6 months)
Rates of hypogammaglobulinemia, defined as IgG levels of <500
Hypogammaglobulinemia is defined as IgG levels of \<500.
Time frame: Up to 60 months
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