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Jaktinib for the Treatment of Ruxolitinib Intolerance of Myelofibrosis

Primary Purpose

Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis(Post-PV MF), Post-essential Thrombocythemia Myelofibrosis(Post-ET MF)

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Jaktinib hydrochloride tablets
Sponsored by
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Myelofibrosis (PMF)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age greater than or equal to 18 years old ,male or female;
  2. Patients diagnosed with Primary Myelofibrosis according to WHO standard (2016 version), or patients diagnosed with Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis according to International Working Group Myeloproliferative Neoplasms Research and Treatment(IWG-MRT) standard. Both Janus Kinase 2(JAK2)mutation and JAK2 wild can be enrolled;
  3. According to Dynamic International Prognostic Scoring System plus(DIPSS-plus) risk grouping criteria, patients with medium-risk-2 or high-risk myelofibrosis were assessed,Patients with grade 1 medium-risk myelofibrosis with hepatosplenomegaly and no response to existing treatment and requiring treatment can also be enrolled;
  4. Patients who have received or are receiving Ruxolitinib,and:Ruxolitinib treatment time is not less than 28 days;Red blood cell transfusion is still needed during treatment with Ruxolitinib;or Ruxolitinib dose (including starting dose and adjusted dose)<20mg bid,And must meet at least one of the following:Level 3 or higher platelet count reduction or Level 3 or higher anemia or Level 3 or higher hematoma/bleeding;
  5. a life expectancy > 24 weeks;
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
  7. Splenomegaly: palpation of the splenic margin to or above the subcostal at least 5cm;
  8. Within 14 days before enrollment,The Laboratory indicators meet the following criteria:

    • Absolute neutrophil count(ANC) > 0.75 x 10^9/L,blood platelet count> 30 x 10^9/L,And no colony stimulating factor was used within 7 days before screening;
    • Peripheral blood blast < 10%;
    • AST和ALT≤3xULN,Patients with severe extramedullary hematopoiesis or who have received iron therapy within 60 days prior to screening and thus have liver function damage,AST和ALT≤5xULN ;
    • Direct bilirubin≤2.0*ULN
    • Creatinine clearance≥45mL/min;
  9. Meet the requirements of the Ethics Committee, voluntarily sign an informed consent form;
  10. Ability to follow research and follow-up procedures;

Exclusion Criteria:

  1. Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (> 250 mg/dL, or 13.9>mmol/L), b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure < 160 mmHg, diastolic pressure < 100 mmHg), c. peripheral neuropathy (NCI - CTC AE v5.0 standard grade 2 or above), etc;
  2. The patients who had a history of congestive heart failure(NCI - CTC AE v5.0 standard grade 3or above), uncontrollable or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism in the first 6 months;
  3. Screening of patients who have surgery within the first 4 weeks;
  4. Screening for patients with arrhythmia requiring treatment or QTc interval (QTcB) >480ms;
  5. Screening for bacterial, viral, parasitic or fungal infections that require treatment;
  6. Patients which have with a history of congenital or acquired hemorrhagic diseases;(Note:With the exception of hematoma which caused by Ruxolitinib)
  7. Splenectomy patients or in the group carried out within three months before the spleen radiation treatment (including internal radiation and external radiation)
  8. Screening HIV, HBV DNA positive or higher than the normal reference range, or HCV RNA positive for HCV antibody;
  9. Women who are planning to become pregnant or who are pregnant or breast- feeding, as well as those who were unable to use effective contraceptives throughout the trial;Male patients who do not use condoms during the administration and within 2 days (approximately 5 half-lives) after the last administration;
  10. Patients who have suffered from malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years; Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected;
  11. With other serious diseases, the researchers think that may affect patient safety or compliance;
  12. The patients who had used the Jakatinib hydrochloride;
  13. Patients who have participated in the clinical trials of other new drugs or medical devices within the first 1 months;
  14. The patients who used the Hematopoietic growth factors within 14 days before Into the group (granulocyte growth factors, or platelet hormone) ;
  15. Patients who cannot cooperate with or cannot perform MRI or CT scans;
  16. Patients with refractory or recurrent myelofibrosis:

    refractory of myelofibrosis:After at least 28 days of adequate administration of JAK inhibitors, the spleen palpation was less than 15% smaller than before administration.Or at least 3 months later, the spleen volume on MRI/CT decreased by <10% compared with that before the administration.

    Recurrence of myelofibrosis: after at least 3 months of taking adequate amount of JAK inhibitor, the spleen was enlarged again after shrinking compared with that before taking the drug, and compared with the minimum value during taking the drug, the spleen volume increased ≥10% on MRI/CT examination or ≥30% on spleen palpation.

  17. Any treatment MF medication (eg hydroxyurea,except ruxolitinib ), any immunomodulation used within 2 weeks prior to enrollment Agent (such as thalidomide), any immunosuppressant, glucocorticoids ≥ 10 mg/day of prednisone or equivalent biological strength, or patients within 6 half-life of the drug, over time Prevail;Patients who had received rucotinib within 1 week prior to enrolling

Sites / Locations

  • The First Affiliated Hospital of Medical School of Zhejiang University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Jaktinib Hydrochloride Tablets 100mg twice a day.

Jaktinib Hydrochloride Tablets 150mg once a day

Jaktinib Hydrochloride Tablets 100mg once a day

Jaktinib Hydrochloride Tablets 200mg once a day

Arm Description

This is the dose group was given Jaktinib Hydrochloride Tablets 100mg (2 tablets)dose group for twice a day.

This is the dose group was given Jaktinib Hydrochloride Tablets 150mg (3 tablets)dose group for once a day.

This is the dose group was given Jaktinib Hydrochloride Tablets 100mg (2 tablets) dose group for once a day

This is the dose group was given Jaktinib Hydrochloride Tablets 200mg (4 tablets)dose group for once a day.

Outcomes

Primary Outcome Measures

Splenic response rate at Week 24
Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline

Secondary Outcome Measures

Objective response rate
IWG-MRT efficacy criteria
Anemia response rate
Proportion of anemia response in all of anemia patients
Total symptoms score(TSS) response rate
TSS response is defined as the proportion of subjects who achieve a ≥ 50% reduction in TSS at the Week 24 compared to baseline
Progression-free survival
The time from the date of enrollment to the date on which any of the following events occurred:①Spleen volume increased by ≥25% compared to the lowest value recorded during the trial including baseline;②Death from any cause
Leukemia-free survival
The time elapsed from the date of enrollment to the date of any of the following events:①The first bone marrow smear shows the date of ≥20% of the original cells;②The first peripheral blood smear showed ≥20% of the original cells and the absolute value of the original cells was ≥1×10^9/L for at least 2 weeks;③Death from any cause。
Overall survival
Time elapsed from the date of enrollment to death from any cause
Adverse event rate
Vital signs, physical examination, blood routine; severity and incidence of adverse events and adverse reactions (NCI-CTCAE V4.03)
Thrombotic event rate
Arterial thrombosis:①Coronary heart disease;②Cerebral arterial thrombosis;③Peripheral arterial occlusive disease:Such as mesenteric artery thrombosis and extremity arterial thrombosis。Venous thrombosis:①Thrombophlebitis;②Deep vein thrombosis;③Pulmonary embolism。Microcirculatory thrombosis: ① thrombotic thrombocytopenic purpura; ② hemolytic uremic syndrome; ③ extracorporeal circulation thrombosis; ④other: such as fulminant purple epilepsy and disseminated intravascular coagulation

Full Information

First Posted
November 10, 2019
Last Updated
April 18, 2023
Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04217993
Brief Title
Jaktinib for the Treatment of Ruxolitinib Intolerance of Myelofibrosis
Official Title
Jaktinib in Intermediate-risk and High-risk Myelofibrosis and Previously Treated With Ruxolitinib
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
January 7, 2020 (Actual)
Primary Completion Date
August 3, 2022 (Actual)
Study Completion Date
August 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Zelgen Biopharmaceuticals Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase IIB, open-label, multicenter study evaluated the efficacy and safety of oral Jaktinib Hydrochloride Tablets in Intermediate-risk and High-risk Myelofibrosis and Previously Treated With Ruxolitinib. The experiment is divided into two parts: dose exploration and extended research.
Detailed Description
dose exploration: It is planned to enroll about 6 subjects. According to the baseline value of platelet count at the time of enrollment, different doses (100mg Qd or 150mg Qd or 200mg Qd or 100mg Bid) of Jaktinib Hydrochloride Tablets will be Treated. The trial is in progress Adjust the dose according to relevant laboratory indicators. When at least one subject has a spleen volume reduction of ≥35% from the baseline, the sponsor and the investigator will jointly decide whether to enter the extended study part. Extended research: It is planned to enroll about 43 subjects, and the initial dosage of Jaktinib Hydrochloride Tablets is planned to be 100mg Bid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis(Post-PV MF), Post-essential Thrombocythemia Myelofibrosis(Post-ET MF)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Jaktinib Hydrochloride Tablets 100mg twice a day.
Arm Type
Experimental
Arm Description
This is the dose group was given Jaktinib Hydrochloride Tablets 100mg (2 tablets)dose group for twice a day.
Arm Title
Jaktinib Hydrochloride Tablets 150mg once a day
Arm Type
Experimental
Arm Description
This is the dose group was given Jaktinib Hydrochloride Tablets 150mg (3 tablets)dose group for once a day.
Arm Title
Jaktinib Hydrochloride Tablets 100mg once a day
Arm Type
Experimental
Arm Description
This is the dose group was given Jaktinib Hydrochloride Tablets 100mg (2 tablets) dose group for once a day
Arm Title
Jaktinib Hydrochloride Tablets 200mg once a day
Arm Type
Experimental
Arm Description
This is the dose group was given Jaktinib Hydrochloride Tablets 200mg (4 tablets)dose group for once a day.
Intervention Type
Drug
Intervention Name(s)
Jaktinib hydrochloride tablets
Other Intervention Name(s)
Jaktinib
Intervention Description
Jaktinib hydrochloride tablets 100mg twice dose group,Jaktinib hydrochloride tablets 150mg qd dose group, Jaktinib hydrochloride tablets 200mg qd dose group and Jaktinib hydrochloride tablets 100mg qd dose group
Primary Outcome Measure Information:
Title
Splenic response rate at Week 24
Description
Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline
Time Frame
week 24
Secondary Outcome Measure Information:
Title
Objective response rate
Description
IWG-MRT efficacy criteria
Time Frame
up to 24 weeks
Title
Anemia response rate
Description
Proportion of anemia response in all of anemia patients
Time Frame
up to 24 weeks
Title
Total symptoms score(TSS) response rate
Description
TSS response is defined as the proportion of subjects who achieve a ≥ 50% reduction in TSS at the Week 24 compared to baseline
Time Frame
up to 24 weeks
Title
Progression-free survival
Description
The time from the date of enrollment to the date on which any of the following events occurred:①Spleen volume increased by ≥25% compared to the lowest value recorded during the trial including baseline;②Death from any cause
Time Frame
up to 24 weeks
Title
Leukemia-free survival
Description
The time elapsed from the date of enrollment to the date of any of the following events:①The first bone marrow smear shows the date of ≥20% of the original cells;②The first peripheral blood smear showed ≥20% of the original cells and the absolute value of the original cells was ≥1×10^9/L for at least 2 weeks;③Death from any cause。
Time Frame
up to 2 years
Title
Overall survival
Description
Time elapsed from the date of enrollment to death from any cause
Time Frame
up to 2 years
Title
Adverse event rate
Description
Vital signs, physical examination, blood routine; severity and incidence of adverse events and adverse reactions (NCI-CTCAE V4.03)
Time Frame
up to 28 weeks
Title
Thrombotic event rate
Description
Arterial thrombosis:①Coronary heart disease;②Cerebral arterial thrombosis;③Peripheral arterial occlusive disease:Such as mesenteric artery thrombosis and extremity arterial thrombosis。Venous thrombosis:①Thrombophlebitis;②Deep vein thrombosis;③Pulmonary embolism。Microcirculatory thrombosis: ① thrombotic thrombocytopenic purpura; ② hemolytic uremic syndrome; ③ extracorporeal circulation thrombosis; ④other: such as fulminant purple epilepsy and disseminated intravascular coagulation
Time Frame
up to 28 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-75 years old (including the threshold value), gender is not limited; Subjects diagnosed with Primary Myelofibrosis according to World Health Organization (WHO) criteria (2016 version), or diagnosed with Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis according to International Working Group Myeloproliferative Neoplasms Research and Treatment(IWG-MRT) standard. Both Janus Kinase 2(JAK2)mutation and JAK2 wild can be enrolled; According to Dynamic International Prognostic Scoring System(DIPSS) , Subjects with intermediate-risk-2 or high-risk myelofibrosis were assessed, Subjects with intermediate-risk-1 myelofibrosis with hepatosplenomegaly and no response to existing treatment and requiring treatment can also be enrolled; Subjects who have received or are receiving Ruxolitinib, and:Ruxolitinib treatment time is not less than 28 days; Red blood cell transfusion is still needed during treatment with Ruxolitinib; or Ruxolitinib dose (including starting dose and adjusted dose)<20mg bid,And must meet at least one of the following:Level 3 or higher platelet count reduction or Level 3 or higher anemia or Level 3 or higher hematoma/bleeding; Life expectancy > 24 weeks; Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 0, 1 or 2; Splenomegaly: palpation of the splenic margin to or above the subcostal at least 5cm; Acceptable laboratory assessments obtained within 14 days prior to enrollment: Absolute neutrophil count(ANC)>0.75 x 10^9/L, blood platelet count>100 x 10^9/L; Peripheral blood blast count < 10%; Aspartate transaminase (AST) and alanine transaminase (ALT)≤3 x the upper limit of the normal range (ULN); Subjects with liver function impairment due to severe extramedullary haematopoiesis or iron removal therapy within 60 days prior to screening, AST and ALT≤5 x ULN; Direct bilirubin≤2.0 x ULN; Calculated creatinine clearance of≥45 mL/min; Meet the requirements of the Ethics Committee, voluntarily sign an informed consent form; Ability to follow research and follow-up procedures. Exclusion Criteria: Any significant clinical or laboratory abnormalities that the investigator considers to affect safety assessment, such as: a. uncontrolled diabetes (> 250 mg/dL, or 13.9>mmol/L); b. had high blood pressure and antihypertensive drug treatment under two or unable to descend to the ranges (systolic blood pressure < 160 mmHg, diastolic pressure < 100 mmHg); c. peripheral neuropathy (NCI-CTC AE v5.0 grade 2 or above), etc; Subjects who had a history of congestive heart failure(NCI-CTC AE v5.0 grade 3 or above), uncontrollable or unstable angina or myocardial infarction, cerebrovascular accident or pulmonary embolism in the first 6 months; Screening of Subjects who have surgery within the first 4 weeks; Screening for Subjects with arrhythmia requiring treatment or QTc interval (QTcB) >480ms; Screening for bacterial, viral, parasitic or fungal infections that require treatment; Patients which have with a history of congenital or acquired hemorrhagic diseases;(Note:With the exception of hematoma which caused by Ruxolitinib) Splenectomy Subjects or in the group carried out within three months before the spleen radiation treatment (including internal radiation and external radiation) Screening HIV, HBV DNA positive or higher than the normal reference range, or HCV RNA positive for HCV antibody; Women who are planning to become pregnant or who are pregnant or breast- feeding, as well as those who were unable to use effective contraceptives throughout the trial;Male patients who do not use condoms during the administration and within 2 days (approximately 5 half-lives) after the last administration; Subjects who have suffered from malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years; Combined with other serious diseases, the researchers believe that patients' safety or compliance may be affected; With other serious diseases, the researchers think that may affect patient safety or compliance; Subjects who had used the Jaktinib; Subjects who have participated in the clinical trials of other new drugs or medical devices within the first 1 months; Subjects who used the Hematopoietic growth factors within 14 days before Into the group (granulocyte growth factors, or platelet hormone) ; Subjects who cannot cooperate with or cannot perform MRI or CT scans; Subjects with refractory or recurrent myelofibrosis: refractory of myelofibrosis:After at least 28 days of adequate administration of JAK inhibitors, the spleen palpation was less than 15% smaller than before administration.Or at least 3 months later, the spleen volume on MRI/CT decreased by <10% compared with that before the administration. Recurrence of myelofibrosis: after at least 3 months of taking adequate amount of JAK inhibitor, the spleen was enlarged again after shrinking compared with that before taking the drug, and compared with the minimum value during taking the drug, the spleen volume increased ≥10% on MRI/CT examination or ≥30% on spleen palpation. Any treatment MF medication (eg hydroxyurea,except ruxolitinib ), any immunomodulation used within 2 weeks prior to enrollment Agent (such as thalidomide), any immunosuppressant, glucocorticoids ≥ 10 mg/day of prednisone or equivalent biological strength, or Subjects within 6 half-life of the drug, over time Prevail; Subjects who had received Ruxolitinib within 1 week prior to enrolling.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Jin, MD
Organizational Affiliation
The First Affiliated Hospital of Medical School of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Medical School of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No plan to share date of the trial

Learn more about this trial

Jaktinib for the Treatment of Ruxolitinib Intolerance of Myelofibrosis

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