Chidamide, Azacitidine Combined With GM Regimen for Relapsed and Refractory DLBCL Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chidamide, Azacitidine Combined With GM(CAGM) Regimen 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or additional 4 cycles of CAGM regimen in patients ineligible for ASCT/CAR-T therapy; whereas, patients with SD/PD were withdrawn from this study.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
20 mg (4 capsules), d1, d4, d8, d11 orally per cycle
Other Names:
Drug: Azacitidine
100mg d1- d5 subcutaneous injection per cycle
Other Names:
Biological: obinutuzumab
1000mg d4 intravenous infusion per cycle
Other Names:
Drug: Liposomal mitoxantrone
20mg/m2 d5 intravenous infusion per cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years.
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At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm).
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Histopathologically confirmed DLBCL.
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Diseases refractory to first-line treatment (including CD20 monoclonal antibody and anthracycline) or relapsed after the last treatment.
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Life expectancy > 3 months.
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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;
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Adequate bone marrow reserve: Hemoglobin ≥8 g/dL; Platelet count ≥75×109/L; Absolute neutrophil value ≥1.0×109/L; Platelet count ≥50×109/L, absolute neutrophil value ≥0.75×109/L if there is bone marrow invasion.
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The patient has the ability to understand and is willing to provide written informed consent.
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Agreement to practice birth control from the time of enrollment until the follow-up period of the study.
Exclusion Criteria:
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Severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal);
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Structural heart disease, leading to clinical symptoms or abnormal cardiac function (NYHA ≥ grade 2);
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Uncontrolled active infection;
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Concurrent presence of other tumors requiring treatment or intervention;
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Current or expected need for systemic corticosteroid therapy;
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Pregnant or lactating women.
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Other psychological conditions that prevent patients from participating in the research or signing the informed consent.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | the First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Jinzm003