Phase 1: MDS with anemia and low blasts complicated by myelofibrosis
Conditions
Interventions
Phase 2: Lower-risk MDS group with anemia.:Gecacitinib
Phase 1, Group 2: MDS with myelofibrosis or MDS/MPN with myelofibrosis (blasts 5~19%).:Gecacitinib
Phase 1, Group 1: MDS with myelofibrosis or MDS/MPN with myelofibrosis (blasts <5%).:Gecacitinib
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: 1. Age >=18, male and female; 2. Stage 1 patients with MDS-LB or MDS-IB with myelofibrosis or MDS/MPN with myelofibrosis diagnosed according to WHO 5th edition, and Stage 2 patients with MDS diagnosed according to WHO 5th edition and diagnosed according to the International Prognostic Scoring System, Revised (IPSS-R) in the lower-risk groups: the IPSS-R very-low-risk group, the low-risk group, and the intermediate-risk group (24 weeks; 7. ECOG score 0-2; 8. for patients in phase 1 group 2 bone marrow primitive cells 5%-19%, for patients in phase 1 group 1 and phase 2 patients bone marrow primitive cells = grade 2 or diffuse grade 1 for patients in all groups in stage 1; 10. neutrophils >= 1.0 x 10^9/L; 11. platelet count >= 50 x 10^9/L; 12. No previous treatment with JAK inhibitors; 13. Normal major organ function 14 days prior to enrolment, i.e. meeting the following criteria: ALT and AST <= 2.5 x ULN; DBIL and TBIL <= 2.0 x ULN; serum creatinine <= 1.5 x ULN; 14. Comply with the requirements of the Ethics Committee and sign the informed consent voluntarily; 15. able to comply with the study and follow-up procedures.
Exclusion criteria
Exclusion criteria: 1.MDS with isolated del(5q) (MDS-5q-); 2.History of organ transplantation or allogeneic hematopoietic stem cell transplantation; 3.High transfusion burden (HTD): =8 units of RBCs within 16 weeks and =4 units of RBCs within 8 weeks. 4.Diagnosis of acute myeloid leukemia (AML), including acute promyelocytic leukemia and extramedullary acute myeloid leukemia. 5.Any significant clinical and laboratory abnormality which, in the opinion of the investigator, may affect the safety evaluation: a. Uncontrolled diabetes (> 250 mg/dL or > 13.9 mmol/L); b. Hypertension that cannot return to the following range (systolic blood pressure < 160 mmHg, diastolic blood pressure < 100 mmHg); c. Peripheral neuropathy (NCI-CTC AE v5.0 = Grade 2); 6.Patients with a history of congestive heart failure (NCI-CTCAE v5.0 = Grade 3), uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 24 weeks prior to screening; 7.Patients requiring surgical operation within 4 weeks prior to screening; 8.Patients with arrhythmic disorders requiring treatment at the time of screening (except for digoxin). 9.Patients with clinical symptoms of active bacterial, viral, parasitic, or fungal infections requiring treatment during screening; 10.Screening period chest X-ray suggests active pulmonary infections requiring treatment; 11.Patients with a confirmed history of active tuberculosis infection or a positive interferon-gamma release assay during the screening period, confirmed by the investigator as indicative of active tuberculosis infection. 12.HIV antibody positive, HBsAg positive and HBV-DNA positive or above the normal reference range, HCV antibody and HCV-RNA positive during screening period; 13.Patients with epilepsy or those using psychotropic or sedative medications at the time of screening (Note: Except for Estazolam tablets). 14.Female patients who are getting pregnant, already pregnant or breastfeeding, as well as patients who are unable to adopt effective contraceptive measures during the entire course of the trial; male patients who do not use condoms during treatment and for 2 days (around 5 half-lives) after the last dose; 15.Patients with malignant tumors within the past 5 years (except for basal cell carcinomas and cervical cancer in situ that have been cured); 16.Patients with other serious diseases that investigators deem may affect safety or compliance; 17.Suspected allergy to Gecacitinib Hydrochloride or drugs of the same class. 18.Patients who have participated in another clinical trial involving a new drug or medical device and used the investigator drug or medical device within 12 weeks before enrollment. 19.Use of any medication for the treatment of MDS within 2 weeks prior to enrollment; 20.Patients with a history of congenital or acquired bleeding disorders; 21.For any other reasons, the investigator believes that patients are not suitable for inclusion in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving HI-E; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to response.;Proportion of patients achieving the IWG 2018 HI-E criteria.;Change from baseline in the average levels of hepcidin, serum erythropoietin (EPO), ferritin, and red blood cell (RBC) lifespan during the treatment period.;The longest consecutive duration during which the average hemoglobin value increases by =15 g/L from baseline (excluding the influence of transfusions).;Change from baseline in the MDS Frailty Scale-15 (MDS FS-15) score during the treatment period.;overall response rate(ORR);Change in mean hemoglobin levels during treatment compared to baseline.;Duration of response.;safety; | — |
Countries
China
Contacts
Public ContactBing Li
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Outcome results
None listed