EUCTR2020-002393-27-BG进行中（未招募）1 期
A Phase 2, Open-label, Multicenter Study of TL-895 in Subjects with Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis and Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 184
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
- •The inclusion criteria mentioned below are applicable to all cohorts unless otherwise specified.
- •1. Adults =18 years of age who are able to provide informed consent
- •2. Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
- •3. High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
- •4. Cohort 1 (relapsed/refractory MF) (closed for enrollment)- Must have relapsed or refractory MF following JAKi treatment.
- •Relapsed MF is defined as 1 of the following:
- •a. Spleen volume increase by =25% by radiographic imaging from nadir
- •b. A =100% increase in palpable distance below the left lower coastal margin (LLCM) from nadir, for baseline splenomegaly of 5 to 10 cm
- •c. A =50% increase in palpable distance below the LLCM from nadir, for baseline splenomegaly of >10 cm
- •d. Regrowth after achieving complete response
- •Refractory MF is defined as 1 of the following after receiving =12 weeks of JAKi treatment:
- •e. <10% spleen volume reduction by radiographic imaging
- •f. <30% decrease from baseline in spleen size by palpation
- •5. Cohort 2 (JAKi intolerant MF) (closed for enrollment after approval of
- •Amendment 4) - Must have received JAKi treatment for at least 28 days complicated by one of the following criteria while receiving treatment:
- •a. RBC transfusion requirement (=2 units per month for 2 months)
- •b. Grade = 3 thrombocytopenia, anemia, hematoma, and/or hemorrhage
- •6. Cohort 3 - Must be ineligible for JAKi treatment defined by a platelet
- •count of = 25 and <50 x 109/L (based on the average of 2 platelet assessments performed at least 1 week apart, and without platelet
- •transfusion in the 2 weeks prior to platelet assessments).
- •7. Cohort 4 (JAKi treatment ineligible MF) - Must be ineligible for JAKi
- •treatment with a platelet count of = 15 and < 25 x 109/L (based on the
- •average of 2 platelet assessments performed at least 1 week apart).
- •8. MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 each on the 2 symptoms per MFSAF v4.0
- •9. Eastern Cooperative Oncology Group (ECOG) performance status of =2
- •10. Adequate hematological function independent of myeloid growth factor support for at
- •least 21 days, defined as:
- •a. Absolute neutrophil count (ANC) =1.0 × 109/L
- •b. Platelet count = 50 × 109/L for Cohorts 1 and 2, = 25 and < 50 × 109/L for Cohort 3, and = 15 and < 25 × 109/L for Cohort 4. Platelet count for Cohort 3 and Cohort 4 must be based on the average of 2 platelet assessments performed at least 1 week apart.
- •11. Adequate hepatic function defined by:
- •a. Total bilirubin level within normal limits (WNL); if total bilirubin is > upper limit of normal (ULN) then subjects are eligible if the direct bilirubin is =2.0 x ULN
- •b. Aspartate aminotransferase (AST) =2.5 × ULN, and alanine aminotransferase (ALT) =2.5 × ULN.
- •12. Adequate renal function defined by an estimated creatinine clearance = 30 mL/min according Cockcroft Gault
- •13. 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 a highly effective method of contraception for 1 month and 1 week and male subjects must continue to use a highly effective method of con
排除标准
- •1. Prior treatment with any BTK or BMX inhibitors
- •2. Cohorts 1 and 2 - Prior treatment with JAKi within 28 days prior to first study
- •3. Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
- •4. Prior therapy with:
- •a. Anticancer treatment with chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or with any other anticancer therapy within 28 days prior to first dose of study treatment with the exception
- •of prednisone. Prednisone 5 mg QD may be administered from Day 28
- •until 1 day prior to Cycle 1 Day 1. Subjects on a stable dose of erythroid
- •growth factor support for at least 3 months prior to Cycle 1 Day 1 are
- •eligible for the study.
- •b. Any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to first dose of study treatment. Participation in observational study is permitted.
- •c. Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within 3 months prior to first dose of study treatment
- •d. For Cohorts 3 and 4: Requiring or receiving anticoagulation within 7
- •days of first dose of study treatment. Subjects on anti-platelet therapy
- •can be allowed on study after discussion with and approval by the
- •medical monitor.
- •5. Subjects with a history of bleeding diathesis or major hemorrhage (unrelated to trauma) within 6 months prior to first dose of study treatment.
- •6. Received major surgical intervention within 28 days prior to first dose of study treatment, or history of major organ transplant
- •7. Subjects with indwelling surgical drains (eg, peritoneal, CNS, or
- •8. Subjects with active fever (temperature higher than 38.2°C
- •[100.8°F]) within 14 days prior to the first dose of study treatment
- •9. 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
- •10. 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; unstable ventricular arrhythmia; or psychiatric illness/ social
- •situations that would limit compliance with study requirements
- •11. Grade 2 or higher QTc prolongation (> 480 milliseconds per National
- •Cancer Institute Common Terminology of Adverse Events [v 5.0])
- •12. Subjects with uncontrolled bacterial, fungal, parasitic, tuberculosis
- •(TB), or viral infection. Subjects with acute bacterial infections requiring
- •antibiotic use should not enroll until the infection is stable in the
- •judgement of the treating physician; these subjects may be on
- •antibiotics at time of screening.
- •13. Subjects with active hepatitis B virus (HBV) or hepatitis C virus
- •14. Subjects with known history of human immunodeficiency virus (HIV)
- •15. Other 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 nonmetastatic prostate cancer with
- •normal prostate-specific antigen, in situ breast carcinoma after complete
- •surgical resection, or superficial transitional cell bladder carcinoma
- •16. Requires treatment with proton-pump inhibitors (e.g., omeprazole,
- •esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or
研究者
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