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

Phase 2

Recruiting

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Chidamide; Drug: Azacitidine; Biological: obinutuzumab; Drug: Liposomal mitoxantrone

• Registration Number: NCT05823701
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

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

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.

Study Timeline

• Status Verified: 2022-08
• Study Start: 2022-09-30
• Study First Submitted: 2023-02-27
• Study First Submitted QC: 2023-04-10
• Last Update Submitted: 2023-04-10
• Study First Posted: 2023-04-21
• Last Update Posted: 2023-04-21
• Primary Completion: 2023-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

1. Age ≥ 18 years.
2. At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm).
3. Histopathologically confirmed DLBCL.
4. Diseases refractory to first-line treatment (including CD20 monoclonal antibody and anthracycline) or relapsed after the last treatment.
5. Life expectancy > 3 months.
6. 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;
7. 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.
8. The patient has the ability to understand and is willing to provide written informed consent.
9. Agreement to practice birth control from the time of enrollment until the follow-up period of the study.

Exclusion Criteria

1. Severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal);
2. Structural heart disease, leading to clinical symptoms or abnormal cardiac function (NYHA ≥ grade 2);
3. Uncontrolled active infection;
4. Concurrent presence of other tumors requiring treatment or intervention;
5. Current or expected need for systemic corticosteroid therapy;
6. Pregnant or lactating women.
7. Other psychological conditions that prevent patients from participating in the research or signing the informed consent.
8. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chidamide, Azacitidine Combined With GM(CAGM) Regimen	Chidamide	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.
Chidamide, Azacitidine Combined With GM(CAGM) Regimen	obinutuzumab	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.
Chidamide, Azacitidine Combined With GM(CAGM) Regimen	Liposomal mitoxantrone	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.
Chidamide, Azacitidine Combined With GM(CAGM) Regimen	Azacitidine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

the First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China