This is a Phase I clinical study to evaluate the safety and tolerability, pharmacokinetic characteristics and preliminary efficacy of oral WJ01024 administered as monotherapy and in combination with ruxolitinib in patients with myelofibrosis(MF). The study will be conducted in two phases: Phase IA and Phase IB. Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant). Phase IB is a dose-escalation and dose-expansion study of WJ01024 in combination with ruxolitinib in JAKi-naïve patients with intermediate- or high-risk MF.
Phase IA is a dose-escalation and dose-expansion study of WJ01024 monotherapy in patients with MF after failure of JAK inhibitor (JAKi) therapy (relapsed/refractory/intolerant).Dose escalation is carried out by combining accelerated titration and the traditional 3+3 design. During the accelerated titration phase, if no dose-limiting toxicity (DLT) and no ≥2 episodes of grade ≥2 treatment-related adverse events (TRAEs) occur within the first cycle (DLT observation period), no further subjects are enrolled at that dose level, and the study proceeds to the traditional 3+3 phase starting with the 60 mg group. At present, it is expected that the dose will be increased in four groups . If the researchers elects to explore intermediate doses or higher doses during the trial, adjustments will be made based on the actual situation. It is planned to expand the dosage by two groups. The final expanded dosage will be determined based on emerging safety and efficacy data. Dose escalation is stratified by background therapy (with vs. without background medication). Phase IB involves dose escalation and dose expansion studies of WJ01024 combined with ruxolitinib. Phase IB is planned to be conducted in JAKi-naïve patients with intermediate- or high-risk MF. Initiation of Phase IB requires that the group in Phase IA has completed the DLT observation period. Two combination dose groups are planned. Intermediate or higher doses may be explored at the investigator's discretion.Two combination dose levels are planned for expansion ;final expansion dose(s) will be determined based on emerging safety and efficacy data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
5-20mg BID (dosage per investigator judgement)
Henan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGDLT
Incidence of DLT
Time frame: 12 months
AE
incidence and severity of adverse events(AEs) and serious adverse events(SAEs),as well as abnormal changes in clinical significance laboratory tests and other examinations
Time frame: 4 years
MTD
Evaluate the Maximum tolerated dose
Time frame: 12 months
RP2D
Evaluate the recommended dose for phase II
Time frame: 12 months
Pharmacokinetic (PK) Parameter
The blood concentration of WJ01024
Time frame: 1.5 years
SVR35
Percentage of subjects with spleen volume reduction of ≥35% (SVR35)
Time frame: 4 years
Score in MPN-SAF-TSS
Percentage reduction in Total Symptom Score(TSS) and proportion of subjects achieving ≥50% reduction (TSS50) assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Time frame: 4 years
incidence and severity of adverse events and serious adverse events
incidence and severity of adverse events nd serious adverse events,as well as abnormal changes in clinical significance laboratory tests and other examinations
Time frame: 4 years
ORR:CR + PR + clinical improvement
Overall response rate (ORR, CR + PR + clinical improvement) as determined by the investigator according to IWG-MRT criteria
Time frame: 4 years
LFS
Leukemia-free survival (LFS) as assessed by the investigator
Time frame: 4 years
PFS
Progression free survival (PFS) as assessed by the investigator
Time frame: 4 years
OS
OS
Time frame: 4 years
LDH
Evaluation of changes in serum LDH levels
Time frame: 4 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.