1.Chronic neutrophilic leukemia 2. myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis
Conditions
Interventions
Gecacitinib Group:Gecacitinib hydrochloride tablets
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 18 years of age or older,either male or female; 1.Morphologically confirmed diagnosis of one of the following in accordance with WHO (2022) diagnostic criteria:CNL or MDS/MPN-SF3B1-T; 2.Subjects must have a platelet count of >= 100×10?/L and an ANC of >= 1.0×10?/L at baseline and the study-initiation visit (within 7 days before treatment starts). 3.No plans for stem cell transplantation in the near future; 4.Expected life expectancy is >= 24 weeks; 5.Eastern Cooperative Oncology Group (ECOG) score of 0-2; 6.Peripheral blood blasts <= 5 %; 7.Bone-marrow blasts <= 5 %; 8.Adequate organ function within 7 days before first dose, defined as: ALT and AST <= 2.5 × ULN; DBIL and TBIL <= 2.0 × ULN; serum creatinine <= 1.5 × ULN. 9.Provision of informed consent in accordance with the ethics committee; 10.Able to comply with study and follow-up procedures;
Exclusion criteria
Exclusion criteria: 1.Subjects who have received any chemotherapy, immunomodulatory agents (e.g., lenalidomide, pomalidomide, thalidomide, interferon-a), ruxolitinib, anagrelide, or corticosteroids (>10 mg/day prednisone or equivalent). Subjects on stable-dose hydroxyurea for leukocytosis may continue if the dose has remained unchanged for >= 14 days prior to starting gecacitinib. 2.Subjects who received myeloid growth factors (e.g., G-CSF) within 14 days before the first dose of gecacitinib. 3.Subjects with prior exposure to gecacitinib; 4.Subjects on daily aspirin >150 mg. 5.Any clinically significant laboratory or clinical abnormality that, in the investigator’s opinion, could compromise safety assessment, including: a) Uncontrolled diabetes (glucose >250 mg/dL or >13.9 mmol/L); b) Hypertension not adequately controlled (SBP >= 160 mmHg or DBP >= 100 mmHg) on combination therapy; c) Peripheral neuropathy >= Grade 2 per NCI-CTC AE v5.0. 6.Hepatic or renal impairment at screening defined as: a) Child-Pugh Class B or C; b) Known hepatocellular disease (e.g., HBsAg positive or HBV DNA >200 IU/mL or 1000 copies/mL; anti-HCV positive or HCV RNA positive), cirrhosis, or other significant hepatic disorder; c) Direct bilirubin >= 2 × ULN; d) ALT >2.5 × ULN; e) Serum creatinine >= 1.5 × ULN or calculated CrCl <30 mL/min or requirement for dialysis. 7.Clinically significant cardiac disease (NYHA Class III or IV). 8.Disorders that could markedly impair oral drug absorption (e.g., major gastric disease). 9.Active severe infection (significant bacterial, fungal, parasitic, or viral infection) not resolved. 10.History of active tuberculosis or positive interferon-gamma release assay at screening judged by the investigator to indicate active TB. 11.Positive HIV, active HBV (HBsAg positive plus HBV DNA positive or above LLoQ), or anti-HCV positive with HCV RNA positive at screening. 12.History of epilepsy or use of psycholeptics or sedatives (except eszopiclone). 13.Women who are pregnant, planning pregnancy, breastfeeding, or not using effective contraception; men unwilling to use condoms from first dose until 2 days (˜5 half-lives) after last dose. 14.Active alcohol or drug addiction that could interfere with protocol compliance. 15.Malignancy within 5 years (except adequately treated basal-cell carcinoma or cervical carcinoma in situ). 16.Any other severe condition that, in the investigator’s judgment, could compromise safety or compliance. 17.Known hypersensitivity to gecacitinib HCl or related compounds. 18.Inability to swallow tablets. 19.Participation in another clinical trial of an investigational drug or device within 12 weeks prior to screening and has received the investigational product or used the investigational device.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage reduction in spleen volume;Proportion of patients who have >= 50% reduction in MPN-SAF TSS;Proportion of patients achieving spleen response;Patient's global impression of change (PGIC);safety; | — |
Countries
China
Contacts
Public ContactZhijian Xiao
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Outcome results
None listed