Dose Schedule Investigation of B-Cell Maturation Antigen (BCMA) Bispecific Antibody, Elranatamab, for Treatment of Newly Diagnosed Light Chain Amyloidosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Efficacy of BCMA bispecific in treating newly diagnosed AL Amyloid, as measured by hematologic complete response (hCR) rates
研究概览
简要总结
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 two different dosing schedules 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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed Immunoglobulin Light Chain (AL) amyloidosis who have not received any prior therapy.
- •Participants must have a tissue biopsy demonstrating Congo red positivity with characteristic birefringence on polarized microscopy and immunohistochemistry or mass spectrometry confirming light chain type.
- •Participants must not have any evidence of myeloma defining events based on the International Myeloma Working Group (IMWG) myeloma diagnostic criteria (SLIM-CRAB). This excludes the light chain ratio criteria of involved versus uninvolved free light chains (FLC) over 100 in the absence of CRAB criteria.
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Participants must meet the following organ and marrow function as defined below: Absolute neutrophil count ≥1,000/mcL, Absolute platelet count ≥50,000/mcL, Direct bilirubin ≤1.5 × institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN.
- •Participants must have a clonal plasma cell burden of less than 40%.
- •For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- •Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- •AL Amyloidosis Cardiac stage I, II or IIIa disease based on the 2015 European Modification of the 2004 Standard Mayo Clinic Staging in participants with advanced cardiac involvement (Dispenzieri et al., 2004; Wechalekar et al., 2013) (NT-proBNP <8500 ng/L and troponin criteria per staging system).
- •The effects of Elranatamab on the developing human fetus are unknown. Based on the mechanism of action, Elranatamab may cause fetal harm when administered to a pregnant woman and therefore should not be used during pregnancy. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and until 90 days since the last dose of Elranatamab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of Elranatamab administration.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Willingness to undergo study procedures, including bone marrow biopsies as detailed in the schedule of events.
排除标准
- •Participants who are receiving any other investigational agents for this condition.
- •Participants with Stage IIIB Amyloidosis as defined by the Europeans Revised 2004 Mayo Clinic Criteria.
- •Participants with an active malignancy (including lymphoma) with the following exceptions: adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer; adequately treated stage I cancer from which the participant is currently in remission and has been for over 2 years; low-risk prostate cancer with a Gleason score < 7 and prostate specific antigen < 10ng/mL; other localized, indolent and/or low risk cancer may be permitted.
- •Women who are pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or 4 months following discontinuation of Elranatamab, whichever is longer. Pregnant women are excluded from this study because Elranatamab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Elranatamab, breastfeeding should be discontinued if the mother is treated with Elranatamab.
- •Have any other medical, social or psychological factors that could affect the participant's safety or ability to consent personally or comply with study procedures.
- •Participants with active clinically significant autoimmune diseases.
- •Participants seropositive for the human immunodeficiency virus (HIV).
- •Severe, uncontrolled orthostatic hypotension resulting in syncopal/pre-syncopal events despite optimized medical management (e.g., midodrine, pyridostigmine) and in the absence of volume depletion.
- •Plan for autologous stem cell transplant or solid organ transplant during the first 6 months of protocol therapy.
- •History of acute coronary syndrome or uncontrolled ventricular arrhythmias within 3 months prior to screening.
- •Evidence of Left Ventricular (LV) systolic dysfunction as defined by Left Ventricular Ejection Fraction (LVEF) is < 30% by echocardiogram at Screening per site cardiology interpretation.
- •Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction if a permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) is not placed.
- •QT corrected by Fridericia (QTcF) is > 550 msec on Screening ECG unless they have a PPM/ICD implanted.
- •Screening EKG showing acute myocardial ischemia or active conduction system abnormalities with the exception of any of the following: First degree atrioventricular block; Second degree atrioventricular block Type 1 (Mobitz Type 1/Wenckebach type); Right or left bundle branch block (e.g., Left Bundle Branch Block, Right Bundle Branch Block, Left Anterior Fascicular Block, or Left Posterior Fascicular Block); Atrial fibrillation with a controlled ventricular rate; Bifascicular block assessed as benign by the Investigator
- •Major surgery that required general anesthesia within 4 weeks of randomization or is planning major surgery during the study.
- •NYHA class IV symptoms
- •Participants with a Glomerular Filtration Rate (GFR) <20, unless stable on dialysis for at least 3 months
研究组 & 干预措施
Arm B: SUD followed by Arm B dose scheduling
Participants in Arm B will receive standard step-up dosing (SUD) with one dose a week after SUD, followed by Arm B dose scheduling with a fixed duration of 6 months of BCMA bispecific.
干预措施: BCMA bispecific (Drug)
Arm A: SUD followed by Arm A dose scheduling
Participants in Arm A will receive standard step-up dosing (SUD) with one dose a week after SUD, followed by Arm A dose scheduling with a fixed duration of 6 months of BCMA bispecific.
干预措施: BCMA bispecific (Drug)
结局指标
主要结局
Efficacy of BCMA bispecific in treating newly diagnosed AL Amyloid, as measured by hematologic complete response (hCR) rates
时间窗: At end of therapy (after 6 cycles, up to 6 months)
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.
次要结局
- Time to complete hematologic response (hCR)(Up to 6 months)
- Overall Response rate (ORR)(At end of therapy (after 6 cycles, up to 6 months))
- Duration of hematologic response(Up to 6 months)
- Progression free survival (PFS) rate(Up to 60 months)
- Overall survival(Up to 60 months)
- Percentage of participants who achieve organ response(Up to 60 months)
- Time between the first treatment and first recorded involved organ response(Up to 60 months)
- Major organ deterioration progression free survival (MOD-PFS)(Up to 60 months)
- Hospitalization rate(Up to 60 months)
- Rates of disease(Up to 60 months)
- Minimal Residual Disease (MRD) negativity rates at end of therapy(At end of therapy (after 6 cycles, up to 6 months))
- Minimal Residual Disease (MRD) negativity rates at 24 months(At 24 months)
- Change in Quality of life (QoL)(Baseline, end of treatment (up to 6 months))
- Rates of hypogammaglobulinemia, defined as IgG levels of <500(Up to 60 months)