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
Overview
- Phase
- Phase 2
- Intervention
- PD-1 antibody+ HDAC inhibitor
- Conditions
- Peripheral T-cell Lymphoma
- Sponsor
- Fudan University
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, single-arm, phase 2 study to evaluate the efficacy and safety of Anti-PD-1 antibody(Sintilimab) plus HDAC inhibitor(Chidamide) in patients with relapsed/refractory peripheral T-cell lymphoma (r/r PTCL).
Detailed Description
Peripheral T-cell lymphoma accounts for 12-15% of non-Hodgkin's lymphomas in western countries, however, this number is up to 35% or more in some Asian countries, including China. According to the 2016 World Health Organization annual classification, there are 29 subtypes of peripheral T cell lymphoma, among which the most common types are peripheral T cell lymphoma non-specific type (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL). For r/r PTCL, the prognosis was poor with objective response rate range from 8-50% and median progression free survival（PFS）range from 3.2-5 months for chemotherapy. Thus, the treatment of this patient population remained clinically unmet need. This clinical trial will be conducted under Simon's optimal two-stage design. The first stage needs 15 participants, if ≥5 participants acquire remission, the study will move on to the second stage and enroll another 36 patients to achieve a total number of 51 participants enrolled. Drop rate is assumed to be 10%, to insure 47 participants involving the efficacy evaluation statistically. Participants will receive anti-PD-1 antibody plus HDAC inhibitor every three weeks for a cycle, until disease progression or severe/ intolerant toxicity, the maximum treatment period is 2 years.
Investigators
Ji Dongmei
Associate Professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Age range from 18 to 75 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- •Pathologically confirmed relapsed/refractory Peripheral T-cell lymphoma (Including PTCL-NOS, AITL, anaplastic large cell lymphoma（ALTL）, excluding Nature Killer（NK）/T cell lymphoma);
- •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);
- •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;
- •Adequate hepatic function (total serum bilirubin, ALT and AST≤1.5 times of upper limit of normal);
- •Adequate renal function (serum creatinine≤1.5 times the upper limit of normal, creatinine clearence≥50ml/min);
- •Echocardiography or radionuclide cardia functional test, LVEF≥50%;
- •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.
- •Willingness to provide pathological tissue specimens (20 pieces of wax or paraffin tissue sections);
Exclusion Criteria
- •Patients allergic of any drug in this regimen;
- •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);
- •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;
- •Patients who have received grade II or above surgery within 3 weeks before enrollment;
- •History of other malignancy within the past 5 years (except for
- •basal cell carcinoma of the skin and
- •carcinoma in situ of the cervix and
- •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);
- •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;
- •Patients with significant coagulation abnormality;
Arms & Interventions
Sinitilimab+Chidamide
Anti-PD-1 antibody Sintilimab 200mg intravenously every 3 weeks; HDAC inhibitor Chidamide 30mg orally twice every week
Intervention: PD-1 antibody+ HDAC inhibitor
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Up to two years after the start of the study
Time from the data of enrollment to of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free.
Secondary Outcomes
- Overall Survival (OS)(Up to two years after the start of the study)
- incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Since the signing of informed consent forms to 30 days after the last cycle of treatment and 90 days after last dose of anti-PD-1 antibody)