NCT07110844招募中2 期
A Phase 2 Clinical Trial of Teclistamab and Daratumumab in Previously Untreated AL Amyloidosis
Rajshekhar Chakraborty, MD3 个研究点 分布在 1 个国家目标入组 25 人开始时间: 2025年11月7日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Hematologic Complete Response (Heme-CR) rate
研究概览
简要总结
The purpose of this study is to investigate whether teclistamab-daratumumab combination is effective and safe in AL amyloidosis.
The study treatment is divided into cycles (C) and each cycle is 28 days (D). Study treatment is expected to last 6 months.
详细描述
The purpose of this study is to assess the effectiveness and safety of teclistamab-daratumumab combination in newly diagnosed AL amyloidosis. The study aims to evaluate whether this combination is able to effectively decrease the level of toxic amyloid-producing light chains circulating in the participants' blood, with the overarching goal of avoiding organ damage, improving organ function, and prolonging life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years and able to sign Informed Consent Form (ICF). If the individual being considered for participation in this study is unable to provide informed consent due to medical, cognitive, or other conditions, a legally authorized representative (LAR) may consent on their behalf.
- •Ability to comply with the study protocol, in the investigator's judgment.
- •Confirmed histopathological diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) or Immunofluorescence (IF) on a tissue biopsy that is positive for Congo Red.
- •Patient must not have received any prior plasma cell clone-directed therapy.
- •Measurable hematologic disease, defined as one of the following:
- •Difference between involved and uninvolved serum free light chain (dFLC) ≥50 mg/L and/or 5 mg/dL
- •Serum M-protein ≥0.5 g/dL on protein electrophoresis
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •One or more organs involved by AL amyloidosis as per consensus guidelines
- •Pre-treatment clinical laboratory values meeting the following criteria during the screening phase:
- •Absolute neutrophil count ≥0.75 × 10^9/L
- •Hemoglobin level ≥8.0 g/dL; red blood cell transfusion allowed until 7 days before C1D
- •Platelet count ≥50 × 10^9/L; Platelet transfusions are acceptable without restriction during the Screening period
- •Alanine aminotransferase level (ALT) ≤2.5 times the Upper Limit of Normal (ULN)
- •Aspartate aminotransferase (AST) ≤2.5 times the ULN
- •Total bilirubin level ≤1.5 × ULN except for subjects with Gilbert syndrome, in which case direct bilirubin ≤2 × ULN
- •Estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m^2, measured by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs.
- •For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
排除标准
- •Prior therapy for AL amyloidosis or multiple myeloma with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to C1D
- •Patients meeting criteria for symptomatic multiple myeloma by any one of the following: (a) Lytic lesions on imaging (Skeletal survey, whole body CT or MRI, or PET/CT) (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, (d) Bone marrow plasma cell infiltrate of greater than 60%.
- •Patients with involved/uninvolved serum FLC ratio>100 as the sole myeloma-defining event will be allowed.
- •Evidence of significant cardiovascular conditions as specified below:
- •NT-Pro BNP > 8500 pg/mL, and/or
- •NYHA Class IIIb or IV functional class
- •History of other malignancy that could affect compliance with the protocol or interpretation of results.
- •Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.
- •Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
- •Patients on renal replacement therapy
- •Patients with HIV who are not on HAART or those with active hepatitis A, B, or C infection.
- •Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted, as per investigators' discretion.
- •Known hypersensitivity to any of the agents
- •Patients who are receiving any other investigational agent concurrently.
研究组 & 干预措施
Teclistamab-Daratumumab
Experimental
All participants in this study will receive teclistamab and daratumumab.
干预措施: Teclistamab (Drug)
Teclistamab-Daratumumab
Experimental
All participants in this study will receive teclistamab and daratumumab.
干预措施: Daratumumab and Hyaluronidase-fihj (Drug)
结局指标
主要结局
Hematologic Complete Response (Heme-CR) rate
时间窗: 6 months from treatment initiation
Heme-CR will be defined as: involved free light-chain level less than the upper limit of the normal range with negative serum and urine immunofixation; normalization of the uninvolved free light-chain level or free light-chain ratio will not be required to determine a complete response.
次要结局
- Minimal Residual Disease (MRD) negativity rate by Free Light Chain Mass Spectrometry (FLC-MS) in serum(1 month, 3 months, 6 months, and 18 months)
- MRD-negativity rate by multiparameter flow cytometry (MFC) in bone marrow(6 months and 18 months)
- Time to heme-CR(Day 1 of each cycle, and every 6 weeks after treatment cessation (up to 1 year))
- Major organ deterioration-progression-free survival (MOD-PFS) rate(From Cycle 2 to Cycle 6 Day 1 (Each cycle is 28 days), End of treatment visit (up to 6 months from treatment initiation), and up to 18 months from treatment initiation)
- Overall survival rate(Through study completion, up to 18 months from treatment initiation)
- Frequency of Cytokine Release Syndrome (CRS)(Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months))
- Rate of infections(Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months))
- Number of participants with a heart response after treatment(6 months and 18 months)
- Number of No Responses in the heart after treatment(6 months and 18 months)
- Number of Partial Responses (PR) in participants who experienced a heart response after treatment(6 months and 18 months)
- Number of Very Good Partial Responses (VGPR) in participants who experienced a heart response after treatment(6 months and 18 months)
- Number of Complete Response (CR) in participants who experienced a heart response after treatment(6 months and 18 months)
- Number of participants with heart progression after treatment(6 months and 18 months)
- Number of participants with a kidney response after treatment(6 months and 18 months)
- Number of No Responses in the kidneys after treatment(6 months and 18 months)
- Number of Partial Responses (PR) in participants who experienced a kidney response after treatment(6 months and 18 months)
- Number of Very Good Partial Responses (VGPR) in participants who experienced a kidney response after treatment(6 months and 18 months)
- Number of Complete Response (CR) in participants who experienced a kidney response after treatment(6 months and 18 months)
- Number of participants with kidney progression after treatment(6 months and 18 months)
- Number of participants with liver response after treatment(6 months and 18 months)
- Number of No Responses in the liver after treatment(6 months and 18 months)
- Number of Partial Responses (PR) in participants who experienced liver response after treatment(6 months and 18 months)
- Number of Very Good Partial Responses (VGPR) in participants who experienced liver response after treatment(6 months and 18 months)
- Number of Complete Response (CR) in participants who experienced liver response after treatment(6 months and 18 months)
- Number of participants with liver progression after treatment(6 months and 18 months)
研究者
Rajshekhar Chakraborty, MD
Assistant Professor of Medicine
Columbia University
研究点 (3)
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