Evaluation of the Efficacy and Safety of Zeprumetostat in Relapsed/Refractory Large Granular Lymphocyte Leukemia (T-LGLL)
Conditions
Brief summary
This study is a single-arm, prospective, exploratory clinical trial aimed at exploring the efficacy and safety of zeprumetostat in patients with relapsed/refractory large granular T-cell leukemia. The study is expected to enroll 10 patients with relapsed/refractory large granular T-cell leukemia for treatment with zeprumetostat . The patients will undergo a maximum 4-week screening period and then enter the treatment phase, where they will receive zeprumetostat 350mg twice daily orally. The treatment lasts for 28 consecutive days as one cycle. If adverse events occur during the treatment, they will be handled according to the suspension and resumption standards. The efficacy and safety will be evaluated after the patients complete two cycles of administration.
Interventions
DRUGzeprumetostat
The patients will undergo a maximum 4-week screening period and then enter the treatment phase, where they will receive zeprumetostat 350mg twice daily orally. The treatment lasts for 28 consecutive days as one cycle. If adverse events occur during the treatment, they will be handled according to the suspension and resumption standards.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female age ≥ 18 years Diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL) Meet any of the following indications for treatment： 1. Hemoglobin \< 100g/L or RBC transfusion dependence 2. Neutrophil count \<0.5×10\^9/L or neutrophil count decreased with recurrent infection 3. Progressive splenomegaly and/or Massive Splenomegaly 4. Combined with autoimmune diseases requiring treatment, such as rheumatoid arthritis, autoimmune thyroiditis, etc. 5. Severe B symptoms Failure or intolerance to a first-line therapy ECOG performance status ≤2 Expected survival ≥ 6 months Willing and able to comply with the requirements for this study and written informed consent. \-
Exclusion criteria
History of other lymphoproliferative neoplasms Had malignant tumor within 5 years before enrollment, exclusive of cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial tumor, cervical carcinoma in situ or other indolent tumors Previously received organ or stem cell transplantation. Patients with active infection within 2 weeks before giving the first dose of medication Patients with HBV, HCV, HIV or other infections that require treatment History of immunodeficiency, or congenital immunodeficiency disorders Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, including clinically significant cardiac diseases, refractory hypertension, metabolic disorders and other diseases that seriously affect the function of the gastrointestinal tract within the 6 months prior to enrollment. Abnormal liver function: two consecutive examinations with an interval of ≥1 week suggest that ALT and AST are 2.5 times higher than the upper limit of normal values Renal impairment: creatinine clearance \<60ml/min Having a history of mental illness or suffering from severe cerebrovascular diseases or cognitive sequelae History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc. Difficulty in swallowing, chronic diarrhea and intestinal obstruction, there are multiple factors that affect the administration and absorption of medications. Received attenuated vaccine 4 in weeks before enrollment Participation in another clinical trial within 4 weeks before the start of this trial Have an allergy to zeprumetostat or any other part of this medicine. Previously treated with other EZH2 inhibitor. Pregnant or breast-feeding patients Patients considered to be ineligible for the study by the investigator for reasons other than the above \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of achieving hematological remission after two cycles of treatment | 8 weeks | Hematological response is evaluated by hemoglobin (Hb), absolute neutrophil count (ANC), platelet count (PLT), absolute lymphocyte count (ALC), absolute large granular lymphocyte count, and blood transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of adverse reactions during treatment | 8 weeks | Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event |
| The time to achieve partial hematological remission | 8 weeks | HPR is assessed by Hb, ANC, PLT, ALC, absolute large granular lymphocyte count and blood transfusion |
| Time to achieve complete hematologic response | 8 weeks | HCR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count. |
| Time to achieve complete molecular response | 8 weeks | CMR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count |
| Change of the health-related quality of life after two cycles of treatment | Baseline and 2 cycles of therapy (Each cycle is 28 days） | Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) is used to assess the health-related quality of life of patients. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability |
| Time from treatment benefit to disease recurrence | A minimum of 2 years of planned follow-up | Duration time was calculated from response to relapse. |
Outcome results
None listed