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

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Chidamide
Azacitidine
obinutuzumab
Liposomal mitoxantrone
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • the First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chidamide, Azacitidine Combined With GM(CAGM) Regimen

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall response rate(ORR)
The rate of patients who achieved CR or PR after treatment by CAGM regimen
Complete response rate(CRR)
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
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)
PFS will be assessed from the first CAGM given to date of progression, relapse, death or end of follow-up.
Overal survival(OS)
OS will be assessed from the first CAGM given to date of death or end of follow-up.
Overall response rate(ORR)
The rate of patients who achieved CR or PR after treatment by CAGM regimen
Complete response rate(CRR)
The rate of patients who achieved CR after treatment by CAGM regimen

Full Information

First Posted
February 27, 2023
Last Updated
April 10, 2023
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05823701
Brief Title
Chidamide, Azacitidine Combined With GM Regimen for Relapsed and Refractory DLBCL Patients
Official Title
A Phase 2 Study of Chidamide, Azacitidine Combined With GM Regimen for Patients With Relapsed and Refractory DLBCL
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chidamide, Azacitidine Combined With GM(CAGM) Regimen
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Chidamide
Other Intervention Name(s)
Tucidinostat
Intervention Description
20 mg (4 capsules), d1, d4, d8, d11 orally per cycle
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
AZA
Intervention Description
100mg d1- d5 subcutaneous injection per cycle
Intervention Type
Biological
Intervention Name(s)
obinutuzumab
Other Intervention Name(s)
Gazyva
Intervention Description
1000mg d4 intravenous infusion per cycle
Intervention Type
Drug
Intervention Name(s)
Liposomal mitoxantrone
Other Intervention Name(s)
PLM60
Intervention Description
20mg/m2 d5 intravenous infusion per cycle
Primary Outcome Measure Information:
Title
Overall response rate(ORR)
Description
The rate of patients who achieved CR or PR after treatment by CAGM regimen
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Title
Complete response rate(CRR)
Description
The rate of patients who achieved CR after treatment by CAGM regimen
Time Frame
At the end of Cycle 2 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events
Description
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.
Time Frame
initiation of study drug until 30 days after last dose
Title
Progression-free survival(PFS)
Description
PFS will be assessed from the first CAGM given to date of progression, relapse, death or end of follow-up.
Time Frame
Up to 24 months after the end of last patients' treatment.
Title
Overal survival(OS)
Description
OS will be assessed from the first CAGM given to date of death or end of follow-up.
Time Frame
Up to 24 months after the end of last patients' treatment.
Title
Overall response rate(ORR)
Description
The rate of patients who achieved CR or PR after treatment by CAGM regimen
Time Frame
At the end of Cycle 6 (each cycle is 28 days)
Title
Complete response rate(CRR)
Description
The rate of patients who achieved CR after treatment by CAGM regimen
Time Frame
At the end of Cycle 6 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhengming Jin
Phone
67781856
Email
jinzhengming519519@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Changju Qu
Phone
67781856
Email
qcj310@163.com
Facility Information:
Facility Name
the First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhengming Jin

12. IPD Sharing Statement

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

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