EUCTR2020-002393-27-BE进行中（未招募）1 期
A Phase 2, Multicenter Study of TL-895 in Subjects with Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis, or Indolent Systemic Mastocytosis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 231
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
- •Cohorts 1-4:
- •1. Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
- •2. High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
- •3. Cohort 1 (relapsed/refractory MF) (closed for enrolment) - 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 costal margin (LLCM), 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
- •4. Cohort 2 (JAKi intolerant MF) (closed for enrollment) - 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
- •5. 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).
- •6. 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).
- •7. MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0
- •Cohort 5 only:
- •8. Confirmed diagnosis of ISM as defined by WHO diagnostic criteria. Eligibility must be confirmed based on review of past bone marrow pathology report results. If the pathology report is not available, or if a biopsy was never completed, a local biopsy must be completed, and the pathology results evaluated to confirm subject eligibility.
- •9. Subject must have moderate-to-severe symptoms based on minimum mean ISM-TSAF v1.0 TSS over the 14-day eligibility screening period for assessment of TSS. Minimum TSS for eligibility is = 28.
- •10. Subject must have failed to achieve symptom control for 1 or more baseline symptoms measured by the ISM-TSAF, as determined by the Investigator, with at least 1 of the following symptomatic therapies administered for a minimum of 28 days before starting the ISM-TSAF for determination of eligibility:
- •a. H1 blockers
- •b. H2 blockers
- •c. Leukotriene inhibitors
- •d. Cromolyn sodium
- •e. Corticosteroids
- •f. Omalizumab
- •11. The subject’s symptomatic ISM therapies (eg, H1 and H2 blockers) must be stable (same dose, no new medications =14 days before beginning the 14-day ISM-TSAF TSS eligibility assessment).
- •12. For subjects receiving corticosteroids, the dose must be = 20 mg/day prednisone or equivalent, and the dose must be stable for = 14 days before starting the 14-day ISM-TSAF TSS eligibility assessment.
- •All Cohorts (Cohorts 1-5, unless otherwise noted)
- •13. Adults = 18 years of age who can provide informed consent.
- •14. Eastern Cooperative Oncology Group (ECOG) performance statu
排除标准
- •Cohorts 1-4 only:
- •1. Prior treatment with JAKi within 28 days prior to first study treatment.
- •2. Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
- •3. 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.
- •4. Subjects with peripheral blood or bone marrow blast counts = 10% within 28 days prior to first dose of study treatment.
- •5. Subjects who are eligible for an allogeneic hematopoietic stem cell transplantation (HSCT) per the opinion of the investigator and have a donor.
- •Cohort 5 only:
- •6. Prior therapy with a.Avapritinib, bezuclastinib, or BLU-263/elenestinib. b.Any BTKi. c.Any antineoplastic agent including chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, any other antineoplastic agent, or herbal medications or herbal supplements within 28 days prior to starting the ISM-TSAF for determination of eligibility. d. Any investigational agent within 28 days or five half-lives, whichever is longer, prior to starting the ISM-TSAF for determination of eligibility. Participation in an observational study is permitted. e. Radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before starting the ISM-TSAF for determination of eligibility. f. Any hematopoietic growth factor < 14 days before starting the ISM-TSAF for determination of eligibility. g. Any major surgical procedure (minor surgical procedures such as central venous catheter placement and BM biopsy are not considered major surgical procedures) < 14 days before starting the ISM-TSAF for determination of eligibility.
- •7. Subject has a current diagnosis of any of the following WHO systemic mastocytosis subclassifications: a. CM only (ie, without documentation of systemic involvement). b. Smoldering systemic mastocytosis. c. SM-AHN. d.ASM. e. MCL. f. MC sarcoma.
- •8. Subject has been diagnosed with another myeloproliferative disorder (eg, myelodysplastic syndrome, MPN).
- •9. Subject has any of the following organ damage C-findings (Valent 2017) attributable to SM: a. Hepatomegaly with ascites and impaired liver function, cirrhosis, or portal hypertension. b. Palpable splenomegaly with hypersplenism. c. Malabsorption with hypoalbuminemia and significant weight loss. d. Skeletal lesions: large osteolytic lesions with pathologic fractures. e. Life-threatening organ damage in other organ systems caused by MC infiltration in tissues.
- •10.Planned major surgery within 28 days prior to the pre
研究者
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