An Open-Label, Phase 1/2 Study of Melflufen and Dexamethasone for Patients with AL Amyloidosis Following at Least One Prior Line of Therapy

Oncopeptides AB0 个研究点目标入组 46 人开始时间: 2019年8月12日最近更新: 2022年3月28日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Oncopeptides AB
入组人数: 46

研究概览入排标准研究者记录与标识符相似试验

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. Male or female, age 18 years or older at the time of signing the informed consent.
•2.Proven histochemical diagnosis of AL amyloidosis based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence confirmed with appropriate method of typing, e.g. mass spectrometry, immunofluorescence or immunohistochemistry (previous aspirate/biopsy tissue specimen result acceptable).
•3.At least one prior line of therapy, defined as either one non-transplant regimen, one ASCT, or one regimen of induction therapy followed by a single ASCT (without hematologic progression between induction and ASCT). No more than 4 cycles of melphalan containing chemotherapy is allowed.
•4.Measurable hematologic disease as defined by serum differential free light chain (dFLC) concentration = 20 mg/L (dFLC is the difference between amyloid forming [involved] and non-amyloid forming [uninvolved] FLC).
•5.Objectively measurable (cardiac, and/or renal and/or liver) organ amyloid involvement, as defined below (amyloid involvement of at least 1 required). See also Appendix 9:
•a.Cardiac involvement: mean wall thickness >12 mm on echocardiogram, with no other cardiac cause or an elevated NT-ProBNP (>332 ng/L) in the absence of renal failure or atrial fibrillation.
•b.Renal involvement is defined as proteinuria (predominantly albumin) >0.5 g/day in a 24-hour urine collection.
•c.Hepatic involvement: Total liver span >15 cm in the absence of heart failure, or alkaline phosphatase >1.5 times institutional upper limit of normal (ULN).
•Amyloid involvement of other organ systems is allowed, but not required.
•6.ECOG performance status = 2. See Appendix 5.
•7.Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (See Appendix 4).
•8.Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information.
•9.Less than 30% plasma cells in bone marrow aspirate or biopsy.
•10. 12-lead screening safety ECG with PR < 220 msec and QTcF interval of = 470 msec calculated by Fridericia Formula (Appendix 12).
•11.Echocardiogram (ECHO) with left ventricular ejection fraction (LVEF) = 45% in patients with known cardiac amyloidosis involvement.
•12.The following laboratory results must be met:
•Absolute neutrophil count (ANC) = 1,500 cells/mm3 (1.5 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy)
•Platelet count = 100,000 cells/mm3 (100 x 109/L) without required transfusions during the 10 days prior to initiation of therapy).
•Hemoglobin = 9.0 g/dl (RBC transfusions are permitted).
•Total Bilirubin = 1.5 x ULN. Higher value may be accepted in
•participants diagnosed with Gilbert syndrome, if approved by the
•medical monitor.
•AST and ALT = 1.5 x ULN.
•Renal function: Estimated GFR (eGFR) by CKD-EPI formula = 45 mL/min (Appendix 11). 13.Male participant agrees to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 90 days after the last dose of melflufen and refrain from donating sperm during this period.
•Female participant meets one of the following conditions:
•i.Not of child bearing potential as defined in Appendix 4
•ii.Not currently pregnant or breastfeeding and agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 30 days after

排除标准

•1. Amyloidosis due to known mutations of the transthyretin gene or presence of another non-AL amyloidosis.
•2. Cardiac risk stage 3 with NT-pro-BNP >5000 pg/mL (Appendix 7).
•3. Evidence of gastro-intestinal bleeding
•Frank bleeding within 6 months prior to initiation of therapy.
•Positive feces-hemoglobin/ fecal occult blood test within 6 months prior to initiation of therapy if clinically relevant. In case of a positive
•test within the last 6 months, a colonoscopy and upper endoscopy are required to exclude clinically relevant conditions. Should the first examination provide a satisfactory explanation to the GI-bleed, the second examination might be cancelled at the discretion of the investigator
•4. Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by =10,000 cells/mm3 [10 x 109/L] after transfusion of an appropriate dose of platelets)
•5. Medically documented cardiac syncope, NYHA (Appendix 8) Class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant ventricular arrhythmias, or atrioventricular block
•6. Clinically significant finding on 24 h Holter recording performed at screening, including but not limited to high degree AV block (2nd degree type 2 or 3rd degree AV block), ventricular arrythmias and sign of sick sinus syndrome. (Bundle branch block is acceptable if clinically stable for =6 months)
•7. Supine systolic blood pressure <90 mm Hg, or orthostatic hypotension defined as a decrease in systolic blood pressure upon standing of >20 mmHg or symptomatic orthostatic hypotension regardless of the amount of the drop in mmHg, despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion. See Section 8.3.2 for details on the assessment of orthostatic hypotension)
•8. Clinically significant factor X deficiency (in investigator's opinion)
•9. Clinically important autonomic disease (in investigator's opinion)
•10. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
•11. Known active infection that is uncontrolled (including symptomatic or asymptomatic COVID-19) or has required intravenous systemic therapy or has required oral anti-infective treatment within 14 days of initiation of treatment; Other wash out period may be considered after consultation and approval of the medical monitor.
•12. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast, and very-low and low risk prostate cancer in active surveillance as defined in NCCN Guideline: Prostate Cancer (NCCN 2019).
•13. Pregnant or breast-feeding females
•14. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
•15. Known HIV or active hepatitis C viral infection
•16. Known active hepatitis B viral infection (definded as HBsAg+)
•Patients with prior hepatitis B vaccination are permitted (defined as HbsAg-, Anti-HBs+, Anti-HBc-)
•Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consultation of risk of reactivation
•17. Concurrent symptomatic multiple myeloma (definded as presence of bone

研究者

发起方

Oncopeptides AB

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