Anti-PD-1 Antibody Plus Chidamide and Rituximab Regimen in Relapsed or Refractory DLBCL (PCR)

Study Overview
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Brief Summary
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To assess the efficacy and safety of Anti-PD-1 Antibody Plus Chidamide and Rituximab Regimen in the Treatment of Relapsed or Refractory DLBCL

Official Title
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Anti-PD-1 Antibody Plus Chidamide and Rituximab Regimen for the Relapsed or Refractory Diffuse Large B Cell Lymphoma (PCR): a Prospective, Multicenter, Single-Arm, Phase II Trial

Conditions
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Relapsed or Refractory DLBCL

Intervention / Treatment
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* Drug: Anti-PD-1 Antibody Plus Chidamide and Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients: 60-75 years old. Relapsed or Refractory patients Histologically confirmed DLBCL with CD20 positive ECOG physical condition score: 0-1 points for patients. The patients must be with at least one evaluable or measurable lesion meeting LYRIC 2016 criteria. Patients who had received at least 2 cycles of standard first-line rituximab regimens didn't obtain remission or relapsed after remission, or who were unable or unwilling to receive chemotherapy due to illness or severe chemotherapy toxicity. Hematology values must be within the following limits at baseline: Absolute neutrophil count (ANC) ≥1,500 cells/μL. In case bone marrow involvement, ANC≥1,000 cells/μL. Platelets≥75,000 cells/μL. In case bone marrow involvement, platelets≥50,000 cells/μL Hemoglobin≥90 g/L.In case bone marrow involvement, hemoglobin≥70 g/L Biochemical values must be within the following limits at baseline: Alanine aminotransferase#ALT#≤2.5×upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤2.5×ULN Total bilirubin≤1.5×ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin. Serum creatinine ≤2×ULN. LVEF ≥50%, as determined by echocardiography. Each subject (or their legally acceptable representative) must sigh an informed consent form (ICF) indicating that he or she understands the purpose of any procedures for the study and are willing to participate in the study. Thyroid stimulating hormone (TSH) or free Thyroxine (FT4) or free Triiodothyronine (FT3) were within the normal range of ±10%. Expected survival time ≥6 months. No radiotherapy, chemotherapy, targeted therapy or hematopoietic stem cell transplantation within 4 weeks before medication. Exclusion Criteria: Patients with clinically symptomatic CNS metastases (e.g., cerebral edema, need for hormonal intervention, or progression of BRAIN metastases) and/or cancerous meningitis. A history of severe allergies or allergic reactions to drugs mentioned above. Patients with other malignant tumors have undergone radical treatment, except for basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of breast and carcinoma in situ of cervix. History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome. Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA titer (no more than 2500 copies/mL or 1000 IU/mL) andHCV RNA (no more than the lower limit of the detection method) in the row. In addition to active hepatitis B or hepatitis C infections requiring treatment, group trials can be conducted. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 2500 copies/mL or 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group. Inability to swallow, intestinal obstruction, or other factors that affect drug administration and absorption. Received systemic antineoplastic therapy within 28 days before treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine, cytokines, or growth factors that control cancer), etc.. Received major surgery within 28 days before treatment or radiotherapy within 90 days before treatment. Received live vaccination (except influenza attenuated vaccine) within 28 days before treatment. Patients requiring long-term systemic glucocorticoid therapy or other immunosuppressive therapy. Allowing subjects to use local, ocular, intra-articular, intranasal and inhaled glucocorticoid therapy. Patients suffering from uncontrollable comorbid diseases, including but not limited to symptomatic congestive heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or bleeding disorders. Pregnant or lactating women. Patients with a history of interstitial lung disease or non-infectious pneumonia. Subjects who have previously had drug-induced or radioactive non-infectious pneumonia but asymptomatic are allowed to enroll. Any life-threatening disease, physical condition or organ dysfunction according to the researchers' judgment may endanger the safety of the subject or put the clinical research at excessive risk. Any other conditinons that the investigator considers inappropriate for participation in this study

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PD-1 Antibody Plus Chidamide and Rituximab Regimen in Relapsed or Refractory DLBCL<br>Anti-PD-1 Antibody Plus Chidamide and Rituximab Regimen in Relapsed or Refractory DLBCL | Drug: Anti-PD-1 Antibody Plus Chidamide and Rituximab<br>* Anti-PD-1 Antibody 200mg, ivd, D1, every 3 weeks Chidamide 30mg, po,D-1, 4, 8, 11, 15, 18, every 3 weeks Rituximab 375mg/m2, ivd, D1, every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response rate |  | 24 weeks | 
| Objective remission rate |  | 24 weeks | 
| Disease Control Rate |  | 24 weeks | 
| Partial Remission Rate |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | PFS was defined as time from study registration to first disease progression or death whichever occurred first, otherwise subject data were censored at time last known disease free | 2 years | 
| Overall Survival | OS was defined as time from study registration to death, and otherwise censored at time last known alive | 2 years | 
| Percentage of Participants With Adverse Events (AEs) | Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.01 | Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of anti-PD-1 antibody | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Rituximab, Chidamide, Anti-PD-1 Antibody