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First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Sintilimab

Rituximab

About this trial

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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ages≥18 years, ≤ 80 years.
Patients with primary treatment of DLBCL.
Histopathologically confirmed diagnosis of diffuse large B-cell lymphoma.
At least one measurable lesion according to the 2014 Lugano criteria.
ECOG physical status score of 0, 1 or 2.
Laboratory tests meet the following criteria unless judged to be due to lymphoma:
1. Routine blood tests: (in the absence of growth factor support therapy or blood transfusion within 7 days) haemoglobin ≥ 90 g/L, absolute neutrophil value ≥ 1.5 x 109/L, platelet count ≥ 90 x 109/L.
2. Liver biochemistry: serum creatinine ≤ 1.5 x upper limit of normal; total bilirubin ≤ 1.5 x upper limit of normal; glutamate transaminase and glutamic oxalacetic transaminase ≤ 2.5 x upper limit of normal.
3. Coagulation: INR and APTT ≤ 2.5 times the upper limit of normal values.
Consent to use contraception during the trial and for 3 months after its completion.
Expected survival ≥ 3 months.

Exclusion Criteria:

Suffering from other untreated malignant tumours.
Cardiovascular disease that remains unstable under pharmacological control .
With severe interstitial lung disease.
With cognitive impairment.
Patients with uncontrolled autoimmune disease.
Presence of uncontrolled active infection.
Expected survival time < 3 months.
Lactating women and subjects of childbearing age who do not wish to use contraception.
With poor adherence or unable to follow up regularly.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

A: PD-1+R-CHOP

B: R-CHOP

Arm Description

After one cycle of standard R-CHOP chemotherapy, Group A uses Sindilizumab + R-CHOP, with Sindilizumab administered on day 10 post-chemotherapy, scheduled for 5 cycles. After 5 cycles, CR patients in group A continue Sindilizumab treatment for 8 times, once every 21 days.

After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP and plans for 5 cycles. CR patients in group B are followed up for observation.

Outcomes

Primary Outcome Measures

CRR

To assess complete response rate (CRR)

Secondary Outcome Measures

PFS

Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first).

ORR

Objective response rate (ORR)

Defined as the time from the start of treatment to the death of the subject due to any cause.

Full Information

NCT ID

NCT05280626

First Posted

March 6, 2022

Last Updated

March 6, 2022

Sponsor

Innovent Biologics (Suzhou) Co. Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05280626

Brief Title

First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP

Official Title

First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP: a Randomized, Open, Multicenter Clinical Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

March 25, 2022 (Anticipated)

Primary Completion Date

December 31, 2025 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Innovent Biologics (Suzhou) Co. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma。The majority of refractory patients have PD-L1 expression due to P53 mutations, some of which account for about 10% of DLBCL.Our department has found that in refractory DLBCL with high PD-L1 expression, cedilizumab monotherapy is also more effective and has reversed chemotherapy resistance.The aim of this study was to determine whether the addition of sindilizumab to the R-CHOP regimen could improve the objective efficiency of DLBCL patients with P53 mutation with PD-L1 expression and to see if it could prolong patient survival.

Detailed Description

This study is a randomized, open, multicenter clinical study to determine whether the addition of sindilizumab to the R-CHOP regimen could improve the objective efficiency of DLBCL patients with P53 mutation with PD-L1 expression and to see if it could prolong patient survival.In this study, patients with P53 mutation with PD-L1 expressing DLBCL were selected to be randomised 1:1 into 2 groups: group A Sindilizumab + R-CHOP and group B R-CHOP. Sindilizumab was administered on day 10 after chemotherapy to avoid interference from prednisone.At the end of 6 cycles, Group A treatment effective maintenance treatment with Sindilizumab for 6 months as indicated.Each patient's tumour tissue was tested for mutations and ctDNA after allocation, and ctDNA and peripheral blood free PD-L1 levels were monitored dynamically during and after treatment.

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

Parallel Assignment

Model Description

Patients with P53 mutation with PD-L1 expressing DLBCL were randomized 1:1 into 2 groups: Group A Sindilizumab + R-CHOP and Group B R-CHOP, Sindilizumab was administered on day 10 after chemotherapy to avoid interference from prednisone. after 6 cycles, the treatment effective in Group A was maintained with Sindilizumab for 6 months as usual.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

A: PD-1+R-CHOP

Arm Type

Experimental

Arm Description

Arm Title

B: R-CHOP

Arm Type

Active Comparator

Arm Description

After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP and plans for 5 cycles. CR patients in group B are followed up for observation.

Intervention Type

Drug

Intervention Name(s)

Sintilimab

Other Intervention Name(s)

Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone

Intervention Description

After one cycle of standard R-CHOP chemotherapy, Group A uses Sintilimab with R-CHOP, with Sintilimab administered on day 10 post-chemotherapy, scheduled for 5 cycles. After 5 cycles CR patients in group A continue Sindilizumab treatment for 8 times, once every 21 days.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone

Intervention Description

After one cycle of standard R-CHOP chemotherapy, Group B uses R-CHOP for 5 cycles. After 5 cycles, CR patients in group B are followed up for observation.

Primary Outcome Measure Information:

Title

CRR

Description

To assess complete response rate (CRR)

Time Frame

1 year

Secondary Outcome Measure Information:

Title

PFS

Description

Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first).

Time Frame

1 year

Title

ORR

Description

Objective response rate (ORR)

Time Frame

1 year

Title

Description

Defined as the time from the start of treatment to the death of the subject due to any cause.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ages≥18 years, ≤ 80 years. Patients with primary treatment of DLBCL. Histopathologically confirmed diagnosis of diffuse large B-cell lymphoma. At least one measurable lesion according to the 2014 Lugano criteria. ECOG physical status score of 0, 1 or 2. Laboratory tests meet the following criteria unless judged to be due to lymphoma: Routine blood tests: (in the absence of growth factor support therapy or blood transfusion within 7 days) haemoglobin ≥ 90 g/L, absolute neutrophil value ≥ 1.5 x 109/L, platelet count ≥ 90 x 109/L. Liver biochemistry: serum creatinine ≤ 1.5 x upper limit of normal; total bilirubin ≤ 1.5 x upper limit of normal; glutamate transaminase and glutamic oxalacetic transaminase ≤ 2.5 x upper limit of normal. Coagulation: INR and APTT ≤ 2.5 times the upper limit of normal values. Consent to use contraception during the trial and for 3 months after its completion. Expected survival ≥ 3 months. Exclusion Criteria: Suffering from other untreated malignant tumours. Cardiovascular disease that remains unstable under pharmacological control . With severe interstitial lung disease. With cognitive impairment. Patients with uncontrolled autoimmune disease. Presence of uncontrolled active infection. Expected survival time < 3 months. Lactating women and subjects of childbearing age who do not wish to use contraception. With poor adherence or unable to follow up regularly.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xiuhua Sun, Master

Phone

+8617709873631

sxh17709873631@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiuhua Sun, Master

Organizational Affiliation

The Second Affiliated Hospital of Dalian Medical University

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

20548096

Citation

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Results Reference

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PubMed Identifier

18559976

Citation

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Results Reference

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PubMed Identifier

24403232

Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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PubMed Identifier

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Citation

Pascual M, Mena-Varas M, Robles EF, Garcia-Barchino MJ, Panizo C, Hervas-Stubbs S, Alignani D, Sagardoy A, Martinez-Ferrandis JI, Bunting KL, Meier S, Sagaert X, Bagnara D, Guruceaga E, Blanco O, Celay J, Martinez-Baztan A, Casares N, Lasarte JJ, MacCarthy T, Melnick A, Martinez-Climent JA, Roa S. PD-1/PD-L1 immune checkpoint and p53 loss facilitate tumor progression in activated B-cell diffuse large B-cell lymphomas. Blood. 2019 May 30;133(22):2401-2412. doi: 10.1182/blood.2018889931. Epub 2019 Apr 11.

Results Reference

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First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP

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