Combination Therapy With Tazemetostat in Relapsed and Refractory Peripheral T-cell Lymphoma

NCT ID: NCT07209163

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2027-03-31

Brief Summary

In decades, the outcome of patients with peripherial T-cell lymphomas is dismal, especially in relapsed or refractory population. After failure to the frontline treatment, patients have limited treatment options and elderly population usually have no chance to undergo transplantation due to age or comorbidity, etc. EZH2 inhibitor like Tazemetostat or SHR 2554 has been demonstrated its anti-tumor activity in PTCL either alone or in combination with other targeted agents.

This study aims to explore the efficacy and safety of Tazemetostat in combination with Linperlisib/Golidocitinib in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma in the patients with peripheral T-cell lymphoma according to next-generation sequesing results.

Conditions

Peripheral T Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tazemetostat With Linperlisib

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

Tazemetostat 800mg, twice once daily (BID), orally

Linperlisib

Intervention Type: DRUG

In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Linperlisib: 60 mg once daily (QD) and 60 mg QD, orally.

In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Linperlisib RP2D in patients with peripheral T-cell lymphoma with co-RHOA/TET2mut.

Tazemetostat With Golidocitinib

Group Type: EXPERIMENTAL

Tazemetostat

Intervention Type: DRUG

Tazemetostat 800mg, twice once daily (BID), orally

Golidocitinib

Intervention Type: DRUG

In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Lgolidocitinib: 150 mg every other day (QOD) and 150 mg QD, orally.

In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Golidocitinib RP2D in patients with peripheral T-cell lymphoma without co-RHOA/TET2mut.

Interventions

Tazemetostat

Tazemetostat 800mg, twice once daily (BID), orally

Intervention Type: DRUG

Linperlisib

In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Linperlisib: 60 mg once daily (QD) and 60 mg QD, orally.

In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Linperlisib RP2D in patients with peripheral T-cell lymphoma with co-RHOA/TET2mut.

Intervention Type: DRUG

Golidocitinib

In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Lgolidocitinib: 150 mg every other day (QOD) and 150 mg QD, orally.

In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Golidocitinib RP2D in patients with peripheral T-cell lymphoma without co-RHOA/TET2mut.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. fully understood and voluntarily signed the ICF for this study

2. aged ≥ 18 years;

3. patients with R/R PTCL who have received at least one prior systemic therapy.

4. Patients must have at least one measurable lesion by computed tomography (CT)/magnetic resonance imaging (MRI) (longest diameter of lymph node lesions > 1.5 cm or longest diameter of extranodal lesions > 1 cm); evaluable lesions: PET-CT examination showed increased local uptake in lymph nodes or extranodal sites (higher than liver) and imaging characteristics consistent with lymphoma performance

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;

6. Adequate bone marrow function, renal function, liver function: ANC ≥ 1.0 × 109/L, hemoglobin ≥ 8.0 g/dL, platelets ≥ 75 × 109/L Note: if the investigator believes that the patient 's above test values are below the lower limit of the protocol due to lymphoma invading the bone marrow, the patient can be enrolled after assessment.Creatinine clearance > 40 mL/min, calculated by Cockcroft-Gault method: • serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for unconjugated bilirubinemia in Gilbert 's syndrome; • ALP (in the absence of bone disease), ALT, and AST ≤ 3.0 × ULN (in the presence of liver metastases, ≤ 5 × ULN); • international normalized ratio (INR) ≤ 1.5 × ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;

7. Current negative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV), and inactive if positive:

• HBV infected patients with positive hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb)] but negative results of HBV DNA polymerase chain reaction (PCR) test can be enrolled; these patients require continuous antiviral therapy after enrollment and HBV DNA PCR test is performed every cycle;
• Patients with positive HCV serology but negative HCV RNA test may be enrolled;
• CMV IgM antibody positive,However, patients who tested negative for CMV DNA could be enrolled;

8. female patients of childbearing potential had to agree to use a double contraception method at least 28 days before starting study drug, during treatment, and for 6 months after the last dose of study drug, and male patients with partners of childbearing potential had to also use an effective double contraception method during the study and for 3 months after the last dose of study drug, e.g., condom, sponge plug, foam, contraceptive jelly, diaphragm cap or intrauterine contraceptive device, contraceptive pills (oral or parenteral), contraceptive implant (Implanon ®), injectable intravascular injection, or other contraceptive measures.Postmenopausal women (> 45 years of age and amenorrheic for > 1 year) and surgically sterile women are exempt from this criterion.

Exclusion Criteria

1. previously used drugs in the treatment regimen may affect the efficacy evaluation of this study (assessed by the investigator)

2. previous bone marrow malignancies, including MDS, AML, MPN, etc.

3. and have clinically significant abnormal test results as judged by the investigator;

4. inability to be orally administered, previous surgical history or severe gastrointestinal diseases such as dysphagia, active gastric ulcer, etc., which the investigator believes may affect the absorption of the study drug;

5. major surgery within 4 weeks before the first study drug administration (referring to grade 3 and 4 surgery as specified in the Measures for the Administration of Clinical Application of Medical Technology implemented on May 1, 2009);

6. current clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, congestive heart failure, any grade 3 or 4 heart disease defined by the New York Heart Association functional classification, or a history of myocardial infarction within 6 months after screening.Left ventricular ejection fraction < 50% measured by echocardiography

7. Venous thrombosis or pulmonary embolism within 3 months before study drug administration;

8. History of stroke or intracranial hemorrhage within 6 months before the first study drug administration;

9. Active infection requiring systemic treatment;

10. History of inflammatory bowel disease (eg, Crohn 's disease or ulcerative colitis);

11. Known hypersensitivity to study drug;

12. Any other disease, metabolic abnormality, physical examination abnormality, or laboratory abnormality of significant clinical significance that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that would make the use of the study drug inappropriate or would compromise the interpretation of the study results or put the patient at high risk.

13. pregnant (positive pregnancy test) or lactating women;

14. patients who have had previous organ transplantation;

15. diagnosed or treated for malignancies other than PTCL, with the following exceptions: a) malignancies treated with curative therapy ≥ 3 years before randomization and without known active disease; b) adequately treated non-melanoma skin cancer or malignancies without evidence of disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

First Deputy Director, Hematology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Mingci Cai, MD

Role: CONTACT

cmc_girl@163.com

02164370045 ext. 665257

Shu Cheng, MD

Role: CONTACT

02164370045 ext. 665257

Other Identifiers

PTCL-EZH2

Identifier Type: -

Identifier Source: org_study_id