Efficacy of Daratumumab Combined With Bortezomib and Dexamethasone in Patients With Mayo 04 Stage III Light Chain Amyloidosis: a Prospective Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Hematologic very good partial response or better at 3 months after treatment initiation
研究概览
简要总结
Patients with light chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. There is ongoing unmet need for effective therapies to rapidly induce deep hematologic response and decrease the early death rate. Lately, trials of daratumumab in newly-diagnosed and relapsed/refractory AL amyloidosis have shown dramatic response rates. However, the benefits of upfront daratumumab in stage III AL patients, especially stage IIIb patients, have not yet been demonstrated definitely in prospective studies. Therefore, we designed a phase II, single arm clinical trial to investigate the efficacy and safety of co-administration of daratumumab with bortezomib and dexamethasone (BD) regimen in treatment-naïve patients with Mayo 04 stage III AL amyloidosis. We planned to enroll 40 patients, who would receive daratumumab and BD treatment for a total duration of 12 months. The primary endpoint is complete response and very good partial response at 3 months after treatment initiation. Secondary endpoints include overall survival, organ response and adverse events.
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
- •18 years old adults.
- •Biopsy proved treatment-naïve AL amyloidosis.
- •Mayo 2004 stage III.
- •dFLC > 50mg/L.
- •Patient must provide informed consent.
排除标准
- •Co-morbidity of uncontrolled infection.
- •Co-morbidity of other active malignancy.
- •Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia.
- •Co-morbidity of grade 2 or 3 atrioventricular block.
- •Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia.
- •Seropositive for human immunodeficiency virus.
- •Seropositive for hepatitis B (positive test for HBsAg). Participants with resolved infection (ie, HBsAg negative but positive for anti-HBc and/or anti-HBs) must be screened of HBV-DNA. Those who are PCR positive will be excluded.
- •Seropositive for hepatitis C (except in the setting of a sustained virologic response).
- •Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology Criteria for Adverse Events.
- •Neutrophil <1×10E9/L，hemoglobin < 7g/dL，or platelet < 75×10E9/L.
- •Severely compromised hepatic or renal function: ALT or AST > 2.5 × ULN, total bilirubin > 1.5mg/dL，or eGFR < 40mL/min (those with renal dysfunction due to renal involvement or renal hypoperfusion from cardiac amyloidosis could be included)
研究组 & 干预措施
Dara-BD
Daratumumab combined with bortezomib and dexamethasone
干预措施: Daratumumab (Drug)
Dara-BD
Daratumumab combined with bortezomib and dexamethasone
干预措施: Bortezomib (Drug)
Dara-BD
Daratumumab combined with bortezomib and dexamethasone
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Hematologic very good partial response or better at 3 months after treatment initiation
时间窗: 3 months
Very good partial response or better is defined as complete response or very good partial response. Complete response: normalization of free light chain levels and ratio with negative serum and urine immunofixation electrophoresis. Very good partial response: difference between involved and uninvolved free light chains (dFLC) less than 40 mg/L
次要结局
- Time to liver response(1 year)
- Time to next treatment(2 years)
- Mortality within 1 month from treatment initiation(1 month)
- major organ deterioration progression-free survival(2 years)
- Mortality within 3 months from treatment initiation(3 months)
- Mortality within 6 months from treatment initiation(6 months)
- Hematologic very good partial response or better at 1 month after treatment initiation(1 month)
- Time to renal response(1 year)
- Overall survival(2 years)
- Stringent dFLC response(1 year)
- Time to hematologic response(1 year)
- Organ response at 3 months after treatment initiation(3 months)
- Organ response at 12 months after treatment initiation(12 months)
- Adverse events(treatment initiation to 30 days after last dose of treatment)
- Hematologic very good partial response or better at 6 months after treatment initiation(6 months)
- Hematologic very good partial response or better at 12 months after treatment initiation(12 months)
- Organ response at 6 months after treatment initiation(6 months)
- Time to cardiac response(1 year)