EUCTR2018-004333-33-NL进行中（未招募）1 期
Phase 2 study of daratumumab monotherapy in previously untreated patients with stage 3B light chain (AL) amyloidosis
European Myeloma Network0 个研究点目标入组 40 人开始时间: 2019年7月8日最近更新:
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 40
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Men or women 18 years of age or older.
- •2. Diagnosis of amyloidosis, AL type, based on:
- •a. Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in Congo Red stained tissue specimens (excluding bone marrow) or characteristic electron microscopy appearance
- •b. Measurable disease of amyloid light chain amyloidosis as defined by at least ONE of the following:
- •- serum monoclonal protein =0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation performed at local lab)
- •- serum free light chain (FLC) =2.0 mg/dL (20 mg/L) with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) =2mg/dL (20 mg/L). Serum FLCs will be measured using the Freelite assay at a central laboratory.
- •- Note: Measurable disease by Urine Bence-Jones Proteinuria is not sufficient for study enrolment.
- •c. Cardiac involvement by AL amyloidosis according to consensus guidelines (See ATTACHMENT 3)
- •3. Mayo Stage 3B disease, defined as both A. increased cardiac troponin (hsTnT >54 pg/ml) AND B. increased NT-proBNP = 8500 pg/ml
- •4. For subjects with congestive heart failure, symptoms should be optimally managed and clinically stable with no cardiovascular-related hospitalizations within 2 weeks prior to Cycle 1 Day 1, as assessed by the Principal Investigator. [See also exclusion criteria 3]
- •5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1,2 or 3 (ATTACHMENT 1)
- •6. Subject must have pre-treatment clinical laboratory values meeting the following criteria during the Screening Phase:
- •a. Absolute neutrophil count =1.0 × 109/L;
- •b. Hemoglobin level =8.0 g/dL (=5 mmol/L)
- •c. Platelet count =75 × 109/L; platelet transfusions are NOT acceptable
- •d. Alanine aminotransferase level (ALT) =2.5 x ULN;
- •e. Aspartate aminotransferase (AST) =2.5 x ULN
- •f. Total bilirubin level =1.5 × ULN, except for subjects with history of Gilbert Syndrome, in which case direct bilirubin = 2 × ULN
- •g. Estimated Glomerular Filtration Rate (eGFR) =20 mL/min; Please note that the eGFR is measured by using the CKD-EPI equation
- •7. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse (if this is the preferred and usual lifestyle of the subject) or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner’s vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing and continue for 3 months after discontinuation of daratumumab. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy.
- •8. During the study and for 3 months after receiving the last dose of daratumumab, female subjects must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.
- •9. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g. either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/g
排除标准
- •1.Prior therapy for AL amyloidosis or multiple myeloma with the exception of 160 mg dexamethasone (or equivalent steroid) maximum exposure prior to Cycle 1 Day 1.
- •2.Previous or current diagnosis of symptomatic multiple myeloma including the presence of lytic bone disease, plasmacytomas, = 60% plasma cells in the bone marrow, and/or hypercalcemia.
- •3.Evidence of significant cardiovascular conditions as specified below:
- •a. New York Heart Association (NYHA) classification of heart failure, stages IIIB or IV
- •b. Heart failure that in the opinion of the investigator due to ischemic heart disease or uncorrected valvular disease, and not due to AL amyloid cardiomyopathy.
- •c. Hospitalization for unstable angina or myocardial infarction or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting, all within the last 6 months prior to the first dose
- •d. Subjects with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular (AV) nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/ICD is indicated but will not be placed (subjects who do have a pacemaker/ICD are allowed in the study)
- •e. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec. Subjects who have pacemaker may be included regardless of calculated QTc interval.
- •f. Supine systolic blood pressure <90 mmHg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of >20 mmHg despite medical management in the absence of volume depletion
- •4. Subjects planning to undergo a 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.
- •5. Diagnosed or treated for malignancy other than AL, except:
- •a. Malignancy treated with curative intent and with no known active disease present for =24 months before Cycle 1 Day 1
- •b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •c. Adequately treated carcinoma in situ (e.g. cervical, breast) with no evidence of disease
- •6. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal
- •7. Subject has known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
- •8. Subject is known to be seropositive for human immunodeficiency virus (HIV). HIV positive subjects who are stable on highly active antiretroviral therapy (HAART) with no opportunistic infections within the last 6 months are eligible.
- •9. Subjects known:
- •a. to be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
- •b. seropositive for hepatitis C
- •10. Subject has
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