A Clinical Study on the Efficacy and Safety of Zeprumetostat in Relapsed/Refractory Large Granular Lymphocyte Leukemia

Official title

A Prospective and Exploratory Clinical Study on the Efficacy and Safety of Zeprumetostat in Relapsed/Refractory Large Granular Lymphocyte Leukemia

Overview

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

• Drug 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.

Primary outcome measures

• The proportion of achieving hematological remission after two cycles of treatment [Time frame: 8 weeks]

Secondary outcome measures (6)

• The incidence of adverse reactions during treatment [Time frame: 8 weeks]
• The time to achieve partial hematological remission [Time frame: 8 weeks]
• Time to achieve complete hematologic response [Time frame: 8 weeks]
• Time to achieve complete molecular response [Time frame: 8 weeks]
• Change of the health-related quality of life after two cycles of treatment [Time frame: Baseline and 2 cycles of therapy (Each cycle is 28 days）]
• Time from treatment benefit to disease recurrence [Time frame: A minimum of 2 years of planned follow-up]

Eligibility criteria

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：

• Hemoglobin < 100g/L or RBC transfusion dependence
• Neutrophil count <0.5×10\^9/L or neutrophil count decreased with recurrent infection
• Progressive splenomegaly and/or Massive Splenomegaly
• Combined with autoimmune diseases requiring treatment, such as rheumatoid arthritis, autoimmune thyroiditis, etc.
• 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.

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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

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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07692529 · EZH2-LGLL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗