Clinical Study on Anti-PD-1 Plus Lenalidomide and Azacitidine in Relapsed/Refractory Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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Aim of this study will evaluate the Efficacy and Safety of Anti-PD-1 monoclonal antibody Combined Lenalidomide and Azacitidine in Relapsed/Refractory Peripheral T-cell Lymphoma Patients.

Detailed Description
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Peripheral T-cell lymphomas (PTCLs) are malignancies of immunologically mature T-cells that arise in peripheral lymphoid tissues. Compared with B-cell lymphoma, the treatment methods of PTCL are more limited, the first-line therapy is usually CHOP-like therapy, but the efficacy is poor, 5-year overall survival rate (OS) is only 30%-40%. Anti-PD-1 monoclonal antibody, Lenalidomide and Azacitidine can all have tumor-killing effects, and the three have complementary theoretical basis in the mechanism of action. This study will evaluate the efficacy and safety of Anti-PD-1 monoclonal antibody Combined Lenalidomide and Azacitidine in Relapsed/Refractory Peripheral T-cell Lymphoma patients.

Official Title
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Clinical Study on the Efficacy and Safety of Anti-PD-1 Monoclonal Antibody Combined Lenalidomide and Azacitidine in Relapsed/Refractory Peripheral T-cell Lymphoma

Conditions
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Relapsed/Refractory Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Anti-PD-1 monoclonal antibody
* Drug: Lenalidomide
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological immunohistochemistry or flow cytometry confirmed that R/R PTCL with measurable (diameter greater than 1.5cm) lesions meets any of the following conditions: 1> After 4 courses of standard first-line therapy or 2 courses of more than two-line therapy, the lesions were reduced by <50%; 2> PTCL with disease progression after first-line or induction therapy; 3> After hematopoietic stem cell transplantation, new lesions appear or the size of previously affected lesions increased by more than 50%. Age ≥ 18 years. ECOG≤2分. The main organ functions need to meet the following conditions:Hemogram needs to meet HB ≥70*1012/L，PLT≥50*109/L，NE≥1*109/L；LVEF≥50%;CR≤132umol/l or CCr≥60 ml/min;ALT and AST≤2 times normal range；Lung function≤Level 1;dyspnea(CTCAE v5.0),and blood oxygen saturation without oxygen absorption> 91%. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up one year period of the study. Estimated survival time ≥3 months. Voluntary signing of informed consent. Exclusion Criteria: Accepted major surgery within 4 weeks before treatment. Prior malignancy (other than Relapsed/Refractory Peripheral T-cell Lymphoma), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer,malignant tonsilloma or carcinoma in situ; Patients who have previously received failed allogeneic hematopoietic stem cell transplantation. Have stroke or intracranial hemorrhage within 3 months. Evidence of complications or medical conditions, including but not limited, that may interfere the conduct of the study or place the patient at serious risk:significant cardiovascular disease(class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification、myocardial infarction within 6 months of screening、uncontrolled or symptomatic arrhythmias) and/or significant lung disease. HIV infection and/or active hepatitis B or active hepatitis C. Uncontrolled systemic infection. Pregnant or breasting-feeding women. According to the researchers' judgment, any life-threatening disease, medical condition or organ system dysfunction which can endanger the patient's safety and Interfer with the absorption or metabolism of anti-PD-1 monoclonal antibody plus Lenalidomide and Azacitidine,may put the results of a study at unnecessary risk.

Ages Eligible for Study
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Minimum Age: 18 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 monoclonal antibody+Lenalidomide+Azacitidine<br>Anti-PD-1 monoclonal antibody plus Lenalidomide, Azacitidine | Drug: Anti-PD-1 monoclonal antibody<br>* Anti-PD-1 monoclonal antibody, 200mg i.v d1 (/21d)<br>* Other names: Anti-PD-1 antibody;Drug: Lenalidomide<br>* Lenalidomide 25mg qd po d1-d10 (/21d)<br>* Other names: Immunomodulator;Drug: Azacitidine<br>* Azacitidine 75mg/m2 i.v d1-d7 (/21d)<br>* Other names: 5-Ladakamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival(PFS) | To measure the duration of response to Anti-PD-1 antibody plus Lenalidomide and Azacitidine over a follow-up period of 12 months | up to 12 months | 
| Overall Response Rate (ORR) | To measure the duration of response to Anti-PD-1 antibody plus Lenalidomide and Azacitidine over a follow-up period of 12 months | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Number of patients who achieved complete response after treatment by Anti-PD-1 antibody plus Lenalidomide and Azacitidine | up to 12 months | 
| Duration of Response | Duration of overall response will be assessed from the first Anti-PD-1 antibody plus Lenalidomide and Azacitidine given to progression,death or last follow-up. | up to 12 months | 
| Overall Survival | OS will be assessed from the first Anti-PD-1 antibody plus Lenalidomide and Azacitidine given to death or last follow-up. | up to 12 months | 
| Adverse events profile | Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated | Measured from start of treatment until 28 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-PD-1 monoclonal antibody,Lenalidomide,Azacitidine