A Single-arm Multi-center Trial of BCMA/CD3 Bispecific Antibody for Relapsed/Refractory AL Amyloidosis or Newly Diagnosed AL Amyloidosis With Insufficient Depth of Hematologic Response After Induction Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Hematologic response VGPR or better rate after four cycles
研究概览
简要总结
The goal of this clinical trial is to evaluate the effectiveness and safety of CM-336, which is a BCMA/CD3 BiTE, in patients with relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy.
详细描述
The goal of this clinical trial is to evaluate the effectiveness and safety of CM-336, which is a BCMA/CD3 BiTE, in patients with relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy.
Patients received subcutaneous CM-336 80 mg once weekly in 28-d cycles after two step-up priming doses of 3 mg and 20 mg given on day 1 and day 4 of cycle 1. For patients achieve hematological PR or better after 2 cycles, and hematological VGPR or better after 4 cycles, the treatment regimen will change to 160mg once every 2 weeks (Q2W).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 years or older
- •Biopsy-proven diagnosis of AL amyloidosis, according to the following standard criteria:
- •Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
- •If clinical and laboratory parameters are insufficient to establish AL amyloidosis, or in cases of doubt, amyloid typing may be necessary
- •Provide informed consent form
- •Measurable disease, as defined by serum differential free light-chain concentration (dFLC; defined as the difference between amyloid forming [involved] and nonamyloid forming [uninvolved] free light-chain [FLC]) ≥50 mg/L)
- •Received at least one prior line of therapy
- •Must have been exposed to CD38 mAb
- •Relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy
- •Relapsed is defined as documented progressive disease >60 days after the last dose of prior therapy
- •Refractory is defined as the documented absence of a hematologic response or hematologic progression on or within 60 days after the last dose of prior therapy
- •Insufficient depth of hematologic response is defined as less than hematological PR by 2 cycles or less than hematologic VGPR by 4 cycles
- •Eastern Cooperative Oncology Group performance status ≤3
- •Clinical laboratory values:
- •Absolute neutrophil count ≥1000/µL
- •Platelet count ≥75,000/µL
- •Hemoglobin ≥75g/L
- •Total bilirubin ≤1.5× the upper limit of normal (ULN), except for patients with Gilbert's syndrome (as defined by >80% unconjugated bilirubin and total bilirubin ≤6 mg/dL)
- •Alkaline phosphatase ≤5× ULN
- •Alanine aminotransferase or aspartate aminotransferase ≤3× ULN
- •Calculated creatinine clearance ≥30 mL/min
- •The woman is not breastfeeding, is not pregnant, and agrees not to be pregnant during the study period and for the following 12 months.
- •Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.
排除标准
- •Non-AL amyloidosis, including hereditary amyloidosis
- •Diagnosed with multiple myeloma, according to the International Myeloma Working Group criteria
- •Have been exposed to BCMA-targeted treatment
- •Known intolerance, hypersensitivity, or contraindication to BCMA BiTE cellular products
- •Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy, after excluding AL amyloidosis-related peripheral neuropathy
- •Medically documented cardiac syncope, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease
- •Ongoing or active infection, known HIV-positive status, or active hepatitis B or C infection
- •Women who are pregnant or breastfeeding
- •Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or have not fully recovered from the surgery, or surgery is arranged during the study period
- •Received live attenuated vaccine within 4 weeks prior to study treatment
- •According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent.
- •Necessary medication or supportive therapy is contraindicated with study treatment.
- •Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme.
研究组 & 干预措施
BCMA/CD3 BiTE
干预措施: CM-336 BCMA/CD3 bispecific antibody (Drug)
结局指标
主要结局
Hematologic response VGPR or better rate after four cycles
时间窗: Four months
Hematologic response VGPR or better rate based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as evaluated by an Adjudication Committee (AC)
Adverse events and serious adverse events
时间窗: Up to 2 year
Adverse events (AEs), serious adverse events (SAEs), according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0
次要结局
- Time to hematologic response(Up to 2 year)
- Hematologic best response(Up to 2 year)
- Duration of hematologic response(Up to 2 year)
- Hematologic response rate(Up to 2 year)
- Overall survival(Up to 5 year)
- Progression-free survival(Up to 5 year)
- Vital organ best response(Up to 2 year)
- Vital organ progression-free survival(Up to 2 year)