Combining Sintilimab and Chidamide for treating Peripheral T-cell Lymphoma

A Phase II Study of Anti-Programmed Death-1(PD-1) Antibody Sintilimab Plus Histone Deacetylase(HDAC) Inhibitor Chidamide in Patients With Relapsed/ Refractory Peripheral T-cell Lymphoma

This study is testing a new treatment combining Sintilimab and Chidamide to see if it can help people with relapsed or hard-to-treat peripheral T-cell lymphoma feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: immunotherapy, Sintilimab, chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT04512534 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of combining Sintilimab, an anti-PD-1 antibody, with Chidamide, an HDAC inhibitor, in patients suffering from relapsed or refractory peripheral T-cell lymphoma. Conducted as a single-center, single-arm phase 2 study, it aims to enroll a total of 51 participants, with an initial assessment of 15 patients to determine if the treatment is effective enough to proceed. Participants will receive the treatment every three weeks for up to two years, or until disease progression or intolerable side effects occur. The study is designed to address the significant unmet need for effective therapies in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with pathologically confirmed relapsed or refractory peripheral T-cell lymphoma and adequate organ function.

Not a fit: Patients with other types of lymphoma, such as NK/T cell lymphoma, or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve response rates and outcomes for patients with relapsed or refractory peripheral T-cell lymphoma.

How similar studies have performed: While this approach is novel in this specific context, similar combinations of immunotherapy and targeted therapy have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. Age range from 18 to 75 years;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
3. Pathologically confirmed relapsed/refractory Peripheral T-cell lymphoma (Including PTCL-NOS, AITL, anaplastic large cell lymphoma（ALTL）, excluding Nature Killer（NK）/T cell lymphoma);
4. At least one two-dimensional measurable lesion with a length diameter of at least 1.5cm and vertical diameter of at least 1.0cm (measured by CT or MRI);
5. Adequate medullary hematopoiesis function ( WBC≥3.5×109/L, ANC≥1.5×109/L, PLT≥80×109/L, HB≥90g/L. If the peripheral blood indicators demonstrate abnormal due to bone marrow or spleen invasion by lymphoma, Enrollment decision can be determined by the investigator as appropriate;
6. Adequate hepatic function (total serum bilirubin, ALT and AST≤1.5 times of upper limit of normal);
7. Adequate renal function (serum creatinine≤1.5 times the upper limit of normal, creatinine clearence≥50ml/min);
8. Echocardiography or radionuclide cardia functional test, LVEF≥50%;
9. Patients of child-bearing period agree to use appropriate contraception. The serum pregnancy test of women in childbearing period was negative within 2 weeks before enrollment.
10. Willingness to provide pathological tissue specimens (20 pieces of wax or paraffin tissue sections);
11. Expectation survival time over 3 months;
12. Willingness to provide written informed consent.

Exclusion Criteria:

1. Patients allergic of any drug in this regimen;
2. Previous treatment with anti-PD-1 antibody combined with HDAC inhibitor (Patients only received single agent of treatment regime or sequentially received anti-PD-1 and HDAC inhibitor are allowed to enroll);
3. Patients with clinically significant heart disease, including severe cardiac insufficiency: New York Heart Disease Association (NYHA) grade IV cardiac insufficiency, unstable angina. And myocardial infarction, congestive heart failure, and QTC interphase \> 500ms which occurred before 6 month of screening;
4. Patients who have received grade II or above surgery within 3 weeks before enrollment;
5. History of other malignancy within the past 5 years (except for 1. basal cell carcinoma of the skin and 2. carcinoma in situ of the cervix and 3. patients who had received treatment for the purpose of cure and had not developed a malignant tumor with a known active disease in the previous 5 years);
6. Patients who had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of the enrollment (if patients received small-molecule targeted drug therapy, they could be included in the study if the drug was discontinued for more than 5 half-lives), or had not recovered from the previous toxicity;
7. Patients with significant coagulation abnormality;
8. Patients with autoimmune diseases requiring treatment or with a history of syndrome requiring systemic use of steroid immunosuppressive agents, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc;
9. Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interfere with results interpretation, including uncontrolled diabetes, or pulmonary disease (a history of interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchospasm);
10. Evidence of central nervous system disease;
11. Patients who received the live vaccine within 4 weeks of the start of the enrollment;
12. Patients with hepatitis B (HBV HBsAg positive and HBV-DNA≥105), hepatitis C (HCV) infection (HCV antibody positive and HCV-RNA detectable); And subjects with other acquired or congenital immune deficiency diseases, including but not limited to hiv-infected;
13. Pregnant or lactating women;
14. Patients who have had previous organ transplants (except autologous hematopoietic stem cell transplants);
15. Severe or uncontrolled infections;
16. Patients with history of severe neurological or psychiatric illness, including dementia or epilepsy;
17. Patients with drug abuse, medical, psychological or social conditions that may interfere with the study results or the assessment of the study results;
18. Patients are unsuitable for the enrollment according to investigator's judgement.

Where this trial is running

Shanghai, Shanghai Municipality

• Dongmei Ji — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Dongmei Ji, doctor — Fudan University
• Study coordinator: Dongmei Ji, doctor

Conditions Peripheral T-cell Lymphoma; relapsed/refractory peripheral T-cell lymphoma; PD-1 antibody; HDAC inhibitor; objective response rate; safety profile