Chidamide, Azacitidine Combined With GM Regimen for Relapsed and Refractory DLBCL Patients

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of CAGM regimen in R/R DLBCL patients and to provide a safe and more effective approach for R/R DLBCL patients.

Detailed Description
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The study will start with an initial 2 cycles of induction therapy with CAGM containing chidamide, azacitidine, obinutuzumab and mitoxantrone liposome, orelabrutinib and rituximab，following imaging examinations to evaluate response rates. For patients feasible to CAR-T/ASCT, sequential CAR-T/ASCT treatment was given. For patients who were unable to undergo CAR-T/ASCT, 4 cycles of CAGM immunochemotherapy were carried out. Efficacy and safety of CAGM regimen in R/R DLBCL will be evaluated.

Official Title
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A Phase 2 Study of Chidamide, Azacitidine Combined With GM Regimen for Patients With Relapsed and Refractory DLBCL

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Chidamide
* Drug: Azacitidine
* Biological: obinutuzumab
* Drug: Liposomal mitoxantrone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm). Histopathologically confirmed DLBCL. Diseases refractory to first-line treatment (including CD20 monoclonal antibody and anthracycline) or relapsed after the last treatment. Life expectancy > 3 months. Appropriate organ function: Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and aspartate aminotransferase ≤3 times the upper limit of normal; Renal function: serum creatinine clearance ≥30 mL/min; Lung function: SPO2>91% without oxygen; Adequate bone marrow reserve: Hemoglobin ≥8 g/dL; Platelet count ≥75×10^9/L; Absolute neutrophil value ≥1.0×10^9/L; Platelet count ≥50×10^9/L, absolute neutrophil value ≥0.75×10^9/L if there is bone marrow invasion. The patient has the ability to understand and is willing to provide written informed consent. Agreement to practice birth control from the time of enrollment until the follow-up period of the study. Exclusion Criteria: Severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal); Structural heart disease, leading to clinical symptoms or abnormal cardiac function (NYHA ≥ grade 2); Uncontrolled active infection; Concurrent presence of other tumors requiring treatment or intervention; Current or expected need for systemic corticosteroid therapy; Pregnant or lactating women. Other psychological conditions that prevent patients from participating in the research or signing the informed consent. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or does not meet the requirements for participation in the study.

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: Chidamide, Azacitidine Combined With GM(CAGM) Regimen<br>R/R DLBCL patients were treated with 2 cycles of CAGM regimen including chidamide, azacitidine, obinutuzumab and liposomal mitoxantrone followed by imaging examination. Patients achieved CR/PR were exposed to ASCT/CAR-T therapy or additional 4 cycles of CAGM regimen in patients ineligible for ASCT/CAR-T therapy; whereas, patients with SD/PD were withdrawn from this study. | Drug: Chidamide<br>* 20 mg (4 capsules), d1, d4, d8, d11 orally per cycle<br>* Other names: Tucidinostat;Drug: Azacitidine<br>* 100mg d1- d5 subcutaneous injection per cycle<br>* Other names: AZA;Biological: obinutuzumab<br>* 1000mg d4 intravenous infusion per cycle<br>* Other names: Gazyva;Drug: Liposomal mitoxantrone<br>* 20mg/m2 d5 intravenous infusion per cycle<br>* Other names: PLM60;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate(ORR) | The rate of patients who achieved CR or PR after treatment by CAGM regimen | At the end of Cycle 2 (each cycle is 28 days) | 
| Complete response rate(CRR) | The rate of patients who achieved CR after treatment by CAGM regimen | At the end of Cycle 2 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events | The safety and tolerability of the therapeutic regimen measured by the incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events. | initiation of study drug until 30 days after last dose | 
| Progression-free survival(PFS) | PFS will be assessed from the first CAGM given to date of progression, relapse, death or end of follow-up. | Up to 24 months after the end of last patients' treatment. | 
| Overal survival(OS) | OS will be assessed from the first CAGM given to date of death or end of follow-up. | Up to 24 months after the end of last patients' treatment. | 
| Overall response rate(ORR) | The rate of patients who achieved CR or PR after treatment by CAGM regimen | At the end of Cycle 6 (each cycle is 28 days) | 
| Complete response rate(CRR) | The rate of patients who achieved CR after treatment by CAGM regimen | At the end of Cycle 6 (each cycle is 28 days) |