EUCTR2018-000108-41-ES进行中（未招募）1 期
A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton’s Tyrosine Kinase Inhibitor, SNS 062, in Patients With B-Lymphoid Malignancies.
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 174
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 and women of age =18 years.
- •2) Eastern Cooperative Oncology Group (ECOG) Performance Status of =2
- •3) Histologically confirmed malignancy with relapsed/refractory disease:
- •v) DLBCL-ABC
- •Cohort 1: Patients with CLL/SLL who have received =1 prior regimen that included a covalent BTKi (single agent or in combination) AND
- •relapsed on or following discontinuation of this BTKi-containing
- •have a BTK C481 mutation (=5% VAF)
- •Cohort 2: Patients with CLL/SLL who have received =1 prior regimen that included a covalent BTKi (single agent or in combination) AND
- •relapsed on or following discontinuation of this BTKi-containing regimen
- •do not have a BTK C481 mutation (<5% VAF).
- •Cohort 3: Patients with relapsed or refractory CLL/SLL who have received =2 prior regimens, including having relapsed from a covalent BTKi (single agent or in combination) AND
- •the most recent regimen was not a covalent BTKi
- •have a BTK C481 mutation (=5% VAF).
- •Cohort 4: Patients with CLL/SLL who have received =1 prior regimen where the most recent regimen was a covalent BTKi (single agent or in combination) and discontinued therapy due to BTKi treatment intolerance (ie, discontinued due to AE or unacceptable toxicity as determined by the investigator). Patients must have a need for treatment (inclusion criterion 6) but relapsed or refractory disease is not required.
- •4) For both Phase 1b and 2, availability of a peripheral blood sample and/or a bone marrow aspirate and/or a lymph node biopsy obtained during the screening period for evaluation of predictive/prognostic disease parameters and to determine if there is a BTK C481 mutation or other resistance mutations
- •5) Presence of measurable disease:
- •a) For patients with SLL, MCL, MZL, DLBCL-ABC, or FL: presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (Cheson, 2014)
- •b) For patients with LPL/WM: presence of serum immunoglobulin M (IgM) with a minimum IgM level >2 times the upper limit of normal (ULN) of each institution (but patient does not have symptomatic hyperviscosity syndrome [HVS] and does not require immediate plasmapheresis for control of HVS)
- •6) Current medical need for therapy of the B-cell malignancy
- •7) An interval of =3 half-lives (unless the last therapy was an antibody where 1 half-life or 14 days, whichever is shorter, is acceptable with demonstrated progression by standard guidelines) from the completion of all previous antitumor therapy to the start of study therapy
- •8) All acute toxic effects of any prior antitumor therapy resolved to Grade 1 (or baseline) before the start of study therapy (with the exception of alopecia[Grade 1 or 2 permitted], neurotoxicity [Grade =2 permitted], or selected laboratory parameters [Grade =2 permitted, with exceptions noted below])
- •9) Adequate thyroid function (TSH, free T3, free T4) with or without thyroid replacement (Grade =2)
- •10) Adequate hepatic profile:a) Serum alanine aminotransferase (ALT) =3 × ULN (Grade =1)
- •b) Serum aspartate aminotransferase (AST) =3 × ULN (Grade =1)
- •c) Serum alkaline phosphatase (ALP) =2.5 × ULN (Grade =1)
- •d) Serum bilirubin =1.5 × ULN (Grade =1), except for patients with Gilbert’s disease
- •11) Adequate renal function:
- •a) Estimated creatinine clearance (eClCR) >45 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula [Appendix 3]),
- •b) Measured creatinine clearance >45 mL/minute (assessed with a 24-hour urine c
排除标准
- •1) Transformed disease at time of screening (eg, Richter’s transformation or blastoid variant of MCL)
- •2) Active central nervous system involvement
- •3) History of a second primary malignancy that has progressed or required systemic treatment in the past 2 years. Exceptions that do not require a 2- year remission include:
- •a. Local basal cell or squamous cell carcinoma of the skin
- •b. Carcinoma in situ of the cervix or breast
- •c. Papillary, noninvasive bladder cancer
- •d. Hormone-sensitive prostate cancer with stable prostate-specific antigen (PSA) for =3 months
- •e. Other localized solid tumors in situ or other low-risk cancers may also be exempt after discussion with the sponsor’s medical monitor
- •4) Significant cardiovascular disease
- •a) Myocardial infarction, arterial thromboembolism, or cerebrovascular
- •thromboembolism within 6 months prior to start of study therapy
- •b) Symptomatic angina
- •c) Symptomatic peripheral vascular disease
- •d) New York Heart Association Class =3 congestive heart failure
- •e) Uncontrolled Grade =3 hypertension (diastolic blood pressure =100 mm Hg, or systolic blood pressure =160 mm Hg), despite antihypertensive therapy
- •f) Uncontrolled arrhythmia
- •5) Significant screening ECG abnormalities:
- •a) Left bundle-branch block
- •b) 2nd- or 3rd-degree atrioventricular block Type 2
- •c) Grade =2 bradycardia
- •d) QTc >480 msec
- •6) Gastrointestinal disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that might interfere with drug absorption or with interpretation of gastrointestinal AEs
- •7) Ongoing risk for bleeding due to any of the following:
- •a) Bleeding diathesis
- •b) Known platelet function disorder
- •c) Uncontrolled peptic ulcer disease
- •d) Oral anticoagulation (eg, warfarin, apixaban, rivaroxaban, dabigatran etexilate)
- •e) Heparin, low-molecular-weight heparin, or heparin fractions (eg, enoxaparin, dalteparin, fondaparinux)
- •Note: Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
- •8) Uncontrolled systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy.
- •Note: Patients with localized fungal infections of skin or nails are eligible.
- •9) Previously documented intolerance to a covalent BTKi, as evidenced by discontinuation of covalent BTKi due to AE (applies to Phase 1b, and to Phase 2, until Cohort 4 accrual is initiated)
- •10) Transplant
- •a) Prior solid organ transplant is excluded
- •b) Prior autologous or allogeneic stem-cell transplant is permitted, provided that the patient has been off immunosuppressive therapy for at least 14 days and has no evidence of active graft-versus-host disease (GVHD)
- •11) Pregnancy or breastfeeding
- •12) Major surgery within 4 weeks before the start of study therapy
- •13) Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids, except as noted
- •Note: At screening, patients may be using systemic corticosteroids (at physiologic doses of =10 mg/day of prednisone or equivalent), or topical or inhaled corticosteroids.
- •14) Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to the start of study therapy, or expected requirement for use during study therapy
- •15) Use of substrates of CYP2C8, CYP3A4, CYP2B6, CYP2C9, and CYP2D6 with a narrow therapeutic index within 7 days prior to the start of study therapy, or
研究者
相似试验
进行中（未招募）
1 期
A study to determine the safety profile and recommended dose of SNS-062 for further evaluation of a new cancer agent to treatment relapsed or resistant B-lymphoid cancersMale or female adult patients with an advanced B-Lymphoid malignancies that have relapsed/progressed after appropriate prior therapy and have resistance and/or mutations that may respond to subsequent BTK inhibition using SNS-062.MedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.1Level: HLTClassification code 10047802Term: Waldenstrom's macroglobulinaemiasSystem Organ Class: 100000004851MedDRA version: 20.1Level: LLTClassification code 10008948Term: Chronic leukemiaSystem Organ Class: 100000004864EUCTR2018-000108-41-GBSunesis Pharmaceuticals, Inc.124
进行中（未招募）
1 期
A study to determine the safety profile and recommended dose of SNS-062 for further evaluation of a new cancer agent to treatment relapsed or resistant B-lymphoid cancersMale or female adult patients with an advanced B-Lymphoid malignancies that have relapsed/progressed after appropriate prior therapy and have resistance and/or mutations that may respond to subsequent BTK inhibition using SNS-062.MedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.1Level: HLTClassification code 10047802Term: Waldenstrom's macroglobulinaemiasSystem Organ Class: 100000004851MedDRA version: 21.0Level: LLTClassification code 10008948Term: Chronic leukemiaSystem Organ Class: 100000004864MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 21.1Level: LLTClassification code 10067070Term: Follicular B-cell non-Hodgkin's lymphomaSystem Organ Class: 100000004864EUCTR2018-000108-41-ITSunesis Pharmaceuticals, Inc.124
进行中（未招募）
1 期
A Phase 1b/2 Study of BGB-11417 in Monotherapy and in Various Combinations with Dexamethasone plus Carfilzomib, Dexamethasone plus Daratumumab, and Dexamethasone plus Pomalidomide in Multiple Myelomarelapsed or refractory multiple myelomaMedDRA version: 21.0Level: LLTClassification code: 10028228Term: Multiple myeloma Class: 10029104CTIS2023-507751-30-00Beigene Ltd.211
进行中（未招募）
1 期
A Study of Galunisertib (LY2157299) in Combination With Nivolumab in Advanced Refractory Solid Tumors and in Recurrent or Refractory NSCLC or Hepatocellular Carcinoma.Advanced Refractory SolidTumours (Phase 1b) and in Recurrent or RefractoryNon–Small Cell Lung Cancer or Hepatocellular Carcinoma, (Phase 2)EUCTR2015-002093-20-DEEli Lilly and Company75
已完成
1 期
An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumorseoplasms by SiteJPRN-jRCT2080223834Bristol-Myers Squibb K.K.1,000