Clinical trial NCT04339400: A Study of TQ05105 Tablets in Subjects With Myeloproliferative Neoplasms
Official title: A Single-group, Open-label, Multicenter, Phase I Study of TQ05105 Tablets in Subjects With Myeloproliferative Neoplasms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Myeloproliferative Neoplasms
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQ05105 is a JAK2 inhibitors and can be used to treat JAK2 target-related diseases. The activation of the JAK/STAT pathway is related to abnormal proliferation, obstruction of apoptosis, and differentiation disorder of leukemia cells which is caused by genetic abnormalities and viral infection.


Eligibility criteria: Inclusion Criteria:

* 1.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3; Life expectancy ≥ 3 months.

  2. Diagnosed as Primary Myelofibrosis(PMF), Polycythemia Vera(PV), Essential Thrombocythemia(ET), Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post- Essential Thrombocythemia Myelofibrosis (PET-MF).

  3. Myelofibrosis at intermediate risk -1 and above according to Dynamic International Prognostic Scoring System(DIPSS); PV or ET were resistant or intolerant to hydroxyurea and/or interferon therapy.

  4. Adequate hematology laboratory index. 5.The most prominent part of the spleen ≥ 5cm to the lower edge of the ribs. 6.Bone marrow blasts and peripheral blood blasts \<20%. 7. Appropriate liver and kidney functions. 8.The main blood coagulation function is appropriate. 9. Those who have used other MPN treatment drugs before first dose need to stop exceed 2 weeks. Those who have received major surgery before first dose need to exceed 4 weeks.

  10.No pregnant or breastfeeding women, and a negative pregnancy test. 11.Understood and signed an informed consent form.

Exclusion Criteria:

* 1. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. With exception of non-melanoma, skin cancer, and carcinoma in situ.

  2. Has participated in other anticancer drug clinical trials within 4 weeks. 3. Has multiple factors affecting oral medication. 4. Has drug abuse history that unable to abstain from or mental disorders. 5. Has active hepatitis B or C, or immunodeficiency. 6. Has immunodeficiency. 7. Has arteriovenous thrombosis events within 4 weeks. 8. Has received long-term and large-dose glucocorticoids or other immunosuppressive drugs within 28 days before signed the informed consent form.

  9. Has serious systemic infections. 10. Has uncontrolled cardiovascular disease. 11. Has uncontrolled hypertension. 12. Has serious systemic infections. 13. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Primary outcomes:
measure: Dose Limiting Toxicity(DLT)
timeFrame: Baseline up to 28 days
measure: Maximal tolerance dose (MTD)
timeFrame: Baseline up to 28 days
Secondary outcomes:
measure: Cmax
timeFrame: Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28.
measure: Tmax
timeFrame: Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28.
measure: AUC0-t
timeFrame: Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28.
Other outcomes:
Locations:
city: Chendu
country: China
facility: West China Hospital ,Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Hematology Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
References: