Clinical trial NCT04851535: Study of Jaktinib In Patients With Myelofibrosis Who Were Relapsed or Refractory of Ruxolitinib Treatment.
Official title: A Phase II Study To Evaluate The Efficacy And Safety of Jaktinib Hydrochloride Tablets In Patients With Myelofibrosis Who Were Relapsed or Refractory of Ruxolitinib Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Lead sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2021-04-20
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a phase 2, single-arm, open-label, non-randomised, multicentre, study to evaluate the efficacy and safety of Jaktinib in patients with myelofibrosis who were relapsed or refractory of ruxolitinib treatment.

Detailed description: All subjects will receive a minimum of 6 treatment cycles or 24 weeks (a 28-day treatment cycle is defined as one treatment cycle).

Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily sign the informed consent form (ICF);
* Age ≥ 18 years, either male or female;
* Subjects diagnosed with a PMF according to World Health Organization (WHO) criteria (2016 Edition), or patients diagnosed with a Post-PV-MF or Post-EF-MF according to International Working Group for Myeloproliferative Neoplasms Research and Treatment (2007 IWG-MRT) criteria;
* Subjects with intermediate-2 or high-risk myelofibrosis, or Intermediate-1 myelofibrosis with symptoms according to the Dynamic International Prognostic System (DIPSS) scoring system;
* Subjects are relapsed/refractory to Ruxolitinib:

  1. Relapsed defined as Ruxolitinib treatment for ≥ 3 months, following an initial response, regrowth to \< 10% spleen volume reduction (SVR) by MRI or \< 30% decrease in spleen size by palpation from baseline;
  2. Refractory defined as Ruxolitinib treatment for ≥ 3 months observed inadequate efficacy response: \< 10%volume SVR by MRI or \< 30% decrease in spleen size by palpation from baseline.
* Subject has a measurable splenomegaly: spleen volume of ≥ 450 cm3 by MRI/CT and ≥ 5 cm below left costal margin by palpation spleen measuring;
* Expected life expectancy is greater than 24 weeks;
* Eastern Cooperative Oncology Group (ECOG) performance Score 0-2;
* Laboratory examination within 7 days before the randomization, fulfilling the following criteria:

Neutrophil count ≥ 0.75 x 109/L, platelet count ≥ 75 x 109/L; Peripheral blood blasts ≤ 10%; ALT and AST≤ 3 ULN, DBIL ≤ 2.0 ULN; Serum creatinine ≤ 2.0 ULN.

Exclusion Criteria:

* Subjects who have been previously exposed to Janus kinase (JAK) inhibitors other than Ruxolitinib for a total of\> 2 weeks;
* Subjects who have taken Ruxolitinib or other JAK inhibitor within 1 week prior to screening;
* Subjects with any significant clinical and laboratory abnormalities which may affect the safety evaluation, such as uncontrolled diabetes, uncontrolled hypertension after taking two or more hypotensive drugs or peripheral neuropathy;
* Subjects with congestive heart failure (NCI-CTCAE V5.0) Class II or above, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening;
* Subjects who have a history of chronic or recurrent respiratory diseases, such as: chronic obstructive pulmonary disease, recurrent lung infections, etc., or have a history of lung infections within 3 months before screening, or currently have upper respiratory tract infections that have not recovered;
* Subjects who have not fully recovered from surgical operation within 4 weeks prior to screening;
* Subjects suffering from arrhythmia and requiring treatment, or QTcB \> 480ms at screening;
* Subjects with clinical symptoms of active bacterial, viral, parasitic or fungal infections requiring treatment at screening;
* Subjects who had undergone splenectomy, or received radiotherapy to the spleen within 6 months before screening;
* Subjects with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC);
* Female subjects who are pregnant, currently breastfeeding, planning to become pregnant;
* Subjects who had experienced malignant tumors (except for adequately treated local basal cell or squamous cell carcinoma of the skin and cervical carcinoma in situ that have been cured) or in combination with other serious diseases within the past 5 years;
* Subjects who have participated in another clinical trial of a new drug or medical instrument within 1 month before screening.
* Subjects who have any other conditions that are not specified in the protocol but the investigator believes that they are not suitable for inclusion in this trial.

Primary outcomes:
measure: Spleen Volume Response rate (SVRR) at Week 24
timeFrame: at Week 24
Secondary outcomes:
measure: Clinical Objective Response Rate (complete remission (CR) + partial remission (PR))
timeFrame: Baseline, up to Year 2
measure: Spleen Response
timeFrame: up to Year 2
measure: Anemia Response
timeFrame: up to Year 2
measure: Response rate of MF-related symptoms
timeFrame: Baseline, up to Year 2
measure: Progression free survival (PFS)
timeFrame: From the date of first dose to the earliest date of either increase in spleen volume ≥ 25% from on-study nadir or death, up to Year 2
measure: Leukemia free survival (LFS)
timeFrame: From the date of first dose to the earliest date of either leukemia or death, up to Year 2
measure: Overall survival (OS)
timeFrame: From the date of first dose to the date of death, up to Year 2
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Jie Jin, PhD
role: PRINCIPAL_INVESTIGATOR
References: