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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Evaluation of the Efficacy and Safety of Zeprumetostat in Relapsed/Refractory Large Granular Lymphocyte Leukemia (T-LGLL)
• Intervention / Treatment: Drug: zeprumetostat

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zeprumetostat	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of achieving hematological remission after two cycles of treatment	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse reactions during treatment	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event	8 weeks
The time to achieve partial hematological remission	HPR is assessed by Hb, ANC, PLT, ALC, absolute large granular lymphocyte count and blood transfusion	8 weeks
Time to achieve complete hematologic response	HCR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count.	8 weeks
Time to achieve complete molecular response	CMR is assessed by Hb, ANC, PLT, ALC, and absolute large granular lymphocyte count	8 weeks
Change of the health-related quality of life after two cycles of treatment	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	Baseline and 2 cycles of therapy (Each cycle is 28 days）
Time from treatment benefit to disease recurrence	Duration time was calculated from response to relapse.	A minimum of 2 years of planned follow-up

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): February 26, 2028

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Hemic and Lymphatic Diseases; Leukemia, Large Granular Lymphocytic
• Other Study ID Numbers: EZH2-LGLL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No