Azacytidine, Bendamustine, Piamprizumab in Refractory/Relapsed B-cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is an open label, single arm, phase I/II for patients with r/r Non-Hodgkin's Lymphoma . The purpose is to evaluate the safety and efficacy of the combination with Azacytidine, Bendamustine and Piamprizumab

Official Title
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An Open Label, Single Arm, Phase I/II in the Combination of Azacytidine, Bendamustine and Piamprizumab in Refractory/Relapsed B-cell Non-Hodgkin's

Conditions
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Non-hodgkin Lymphoma,B Cell

Intervention / Treatment
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* Drug: Azacytidine, Bendamustine and Piamprizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤80 years Performance status (ECOG) between 0 and 3. Histologically confirmed B-cell non-Hodgkin lymphoma (NHL), including the following types defined by WHO 2016. Refractory disease or relapsed after treatment with ≥2 lines of chemotherapy and either having failed autologous HSCT or being ineligible for or not consenting to autologous HSCT; or not suitable for CAR T treatment or resistance, progression or relapse after CAR T treatment; or CAR T pre-culturing losers can also be enrolled. Adequate organ function. An adequate bone marrow reserve. Measurable or assessable disease according to theIWG Response Criteria for Malignant Lymphoma(Cheson 2014). Patients in complete remission (CR) with no evidence of disease were not eligible. Informed consent/assent requiring that all patients have the ability to understand and the willingness to provide written informed consent. Life expectancy > 12 weeks. Patients with definite involvement of the gastrointestinal tract, and patients with central nervous system (CNS) by PETCT and MRI involvement were allowed to enrolled in this clinical study. Exclusion Criteria: Pregnant or lactating women. Uncontrolled medical disorders, active bacterial, viral infection or treponema pallidum infection and so on. Requirement for urgent therapy due to tumor mass effects such as respiratory obstruction or blood vessel compression. Current or expected need for systemic corticosteroid therapy. Any organ failure. Patients with a second tumor requiring therapy or intervention. Subjects considered unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation according to the investigator's judgement. Prior organ allograft. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: combination of Azacytidine, Bendamustine and Piamprizumab<br>combination of Azacytidine, Bendamustine and Piamprizumab in Refractory/Relapsed B-cell Non-Hodgkin's Lymphoma, every 28 days | Drug: Azacytidine, Bendamustine and Piamprizumab<br>* Azacytidine by means of subcutaneous injection, Bendamustine and Piamprizumab intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit. | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The ORR is defined as the proportion of patients with a best overall disease response, including complete response (CR) and partial response (PR). | 6 month | 
| Complete Response Rate | CR rate assess by investigators per the 2014 Lugano classification rate of subjects achieved complete response in all evaluable subjects | 6 month |