A Study of TL-895 in Myelofibrosis
- Conditions
- Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible MyelofibrosisMedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-002393-27-PL
- Lead Sponsor
- Telios Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 181
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 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 coastal 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
5. 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
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 for each of 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. 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 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 contraception for 3 months and 1 week. A
1. Prior treatment with any BTK or BMX inhibitors
2. Prior treatment with JAKi within 28 days prior to first study treatment.
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
pleural)
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 (HCV)
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 pantoprazole). Subjects receivi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method