An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined with Ruxolitinib in Janus associated Kinase Inhibitor (JAKi) Treatment-Naïve Myelofibrosis (MF) Subjects and Subjects with MF who have a Suboptimal Response to Ruxolitinib

Telios Pharma, Inc.0 个研究点目标入组 70 人开始时间: 2022年5月30日最近更新: 2023年10月9日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Telios Pharma, Inc.
入组人数: 70

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

入排标准

性别: All

入选标准

•Phase 1b and Phase 2 Cohort 2
•1. Treatment with ruxolitinib for = 12 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to Sponsor approval of the enrollment form
•A stable dose is defined as a ruxolitinib dose that has not required a treatment hold or dose adjustment
•Subjects must be taking a stable dose of ruxolitinib of at least 5 mg BID or 10 mg QD
•Phase 1b and Phase 2 (both cohorts)
•2. Subjects = 18 years of age and able to provide informed consent.
•3. Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
•4. High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
•5. Palpable spleen measuring = 5 cm below the left lower coastal margin (LLCM) or spleen volume of = 450 cm3 by MRI or CT scan assessment
•6. MF symptoms as defined by having at least 2 symptoms with a score of at least 1 each on the MFSAF v4.0
•7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
•8. Adequate hematological function within 7 days (Phase 1b) or 28 days (Phase 2) prior to first dose, independent of growth factor support for at least 7 days, with the exception of pegylated Granulocyte Colony-Stimulating Factor (G CSF) which requires at least 14 days, defined as:
•Absolute neutrophil count (ANC) = 1.0 × 109/L
•Platelet count = 50 × 109/L
•9. Adequate hepatic function within 7 days (Phase 1b) or 28 days (Phase 2) prior to first dose of study treatment defined as:
•Total serum bilirubin = 2.0 x upper limit of normal (ULN). Subjects with known Gilbert’s syndrome or disease-related hemolysis must have a total bilirubin =3.0 × ULN
•Aspartate aminotransferase (AST) = 2.5 × ULN, and alanine aminotransferase (ALT) = 2.5 × ULN.
•10. Adequate renal function within 7 days (Phase 1b) or 28 days (Phase 2) defined as an estimated creatinine clearance = 30 mL/min according to Cockcroft Gault.
•11. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, must both use a highly effective contraception method during the study. In addition, after the last dose of study drug, female subjects must continue to use contraception for 1 month and 1 week and male subjects must continue to use contraception for 3 months and 1 week. A woman is considered of childbearing potential (i.e., fertile, following menarche and until becoming postmenopausal) unless permanently sterile (refer to Appendix 2 of the protocol for additional details).
•Note: Marketed drugs administered concomitantly in this study may have different contraception requirements, including required duration of contraception use. The contraception requirements in the local prescribing guidelines must be followed for all concomitant drugs administered in this study.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 18
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 52

排除标准

•Phase 2 Cohort 1
•1. Prior treatment with any JAKi
•Phase 1b and Phase 2 Cohort 2
•2. Documented disease progression while on ruxolitinib treatment, defined as any of the following:
•=100% increase in palpable distance, below the LLCM from nadir for baseline splenomegaly of 5 to 10 cm while on ruxolitinib, or
•= 50% increase in palpable distance, below the LLCM from nadir, for baseline splenomegaly of >10 cm while on ruxolitinib, or
•=25% increase from nadir in spleen volume by radiographic imaging while on ruxolitinib treatment, or
•Regrowth after achieving complete response
•Phase 1b and Phase 2 (both cohorts)
•3. Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
•4. Prior treatment with a BTK or BMX inhibitor
•5. Chemotherapy, cytoreductive therapy, immune therapy, cytokine therapy or any investigational therapy within 28 days prior to first dose of study treatment. Subjects on hydroxyurea therapy may continue treatment until 1 day prior to the first dose of study drug.
•6. Active participation in other therapeutic clinical trials including supportive care trials
•7. Subjects with a history of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 6 months prior to first dose of study treatment
•8. Major surgery or planned major surgery within 28 days prior to first dose of study treatment.
•9. History of major organ transplant
•10. Having history of difficulty swallowing, gastric or small bowel surgery with history of malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study treatment
•11. Uncontrolled intercurrent illness including, but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; ventricular arrhythmia; history of myocardial infarction within 3 months
•12. Grade 2 or higher QTc prolongation (> 480 milliseconds [ms] per National Cancer Institute Common Terminology of Adverse Events [v 5.0])
•13. Clinically significant bacterial, mycobacterial, fungal, parasitic, or viral infection. Intravenous (IV) antibiotics within 2 weeks prior to first dose of study treatment.
•14. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)
•15. Known infection with HIV
•16. Known hypersensitivity or contraindications to the study drugs or any of their excipients.
•17. History of another malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated non-metastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection or superficial transitional cell bladder carcinoma
•18. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study provided the proton pump inhibitor is discontinued at least 3 days prior to first dose of study drug.
•19. Women who are pregnant or breastfeeding.
•20. Medical condition, serious intercurrent illness, psychiatric condition, or other circumstance (i.e., committed to an institution by judicial or administrative authority) that, in the Investigator's judgment, could jeopardize the subject's safety

研究者

发起方

Telios Pharma, Inc.

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