EUCTR2020-002393-27-IT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 - A Study of TL-895 in Myelofibrosis
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 128
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
- •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) - 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), for baseline splenomegaly of 5 to 10 cm
- •c. A >=50% increase in palpable distance below the LLCM, 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) - 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 (JAKi treatment ineligible MF) - Must be ineligible for JAKi treatment defined by a platelet count of <=50 x 109/L
- •7. Palpable spleen measuring >=5 cm below the LLCM or spleen volume of >=450 cm3 by MRI or CT scan assessment
- •8. MF symptoms as defined by having at least 2 symptoms with a score of at least 1 each on the MFSAF v4.0
- •9. Eastern Cooperative Oncology Group (ECOG) performance status of <=2
- •10. Adequate hematological function independent of growth factor support for at least 7 days with the exception of pegylated granulocyte colony-stimulating factor (G-CSF) and darbepoetin which require 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, and >=25 × 109/L for Cohort 3
- •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 an effective contraception method during the study and
- •continue to use contraception for 60 days after the last dose of study drug. Effective birth control for males is the use of condoms. Effective birth control for females includes (a) combined, estrogen- and
- •progestogen-containing hormonal contraception (oral, intravaginal, transdermal); (b) intrauterine device combined with a barrier method; (c) intrauterine hormone-releasing system combined with a barrier
- •method; (d) bilateral tubal occlusion/ligation; (e) vasectomized partner; (f) sexual abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,
- •symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
排除标准
- •1. Prior treatment with any BTK, BMX, BCR-ABL, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), bromodomain and extraterminal domain (BET) or spleen tyrosine kinase (Syk)
- •2. Cohorts 1 and 2 - Prior treatment with JAKi within 21 days of the Screening MRI/CT scan.
- •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 (except for JAKi
- •[see exclusion #2]). Hydroxyurea may be taken within 1 day of the first dose of study treatment.
- •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
- •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. 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
- •8. 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
- •9. Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0])
- •10. Subjects with uncontrolled bacterial, fungal, parasitic, 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.
- •11. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •12. Subjects with known history of human immunodeficiency virus (HIV)
- •13. 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
- •14. 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.
- •15. Women who are pregnant or breastfeeding.
- •Please refer to Synopsis of Protocol for full list of criteria
研究者
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