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

NCT05280626 | Not Yet Recruiting Phase 2

• 1 other identifier: CIBI308Y047
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• CRR

  To assess complete response rate (CRR)

  1 year

Secondary Outcomes (3)

• PFS

  1 year

• ORR

  1 year

• OS

  1 year

Study Arms (2)

A: PD-1+R-CHOP

EXPERIMENTAL

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.

Drug: Sintilimab; Drug: Rituximab

B: R-CHOP

ACTIVE COMPARATOR

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.

Drug: Rituximab

Interventions

Sintilimab DRUG

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.

Also known as: Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone

A: PD-1+R-CHOP

Rituximab DRUG

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.

Also known as: Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone

A: PD-1+R-CHOP; B: R-CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.: lead

Related Publications (6)

• Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. doi: 10.1182/blood-2010-03-276246. Epub 2010 Jun 14.

  PMID: 20548096 RESULT

• Young KH, Leroy K, Moller MB, Colleoni GW, Sanchez-Beato M, Kerbauy FR, Haioun C, Eickhoff JC, Young AH, Gaulard P, Piris MA, Oberley TD, Rehrauer WM, Kahl BS, Malter JS, Campo E, Delabie J, Gascoyne RD, Rosenwald A, Rimsza L, Huang J, Braziel RM, Jaffe ES, Wilson WH, Staudt LM, Vose JM, Chan WC, Weisenburger DD, Greiner TC. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study. Blood. 2008 Oct 15;112(8):3088-98. doi: 10.1182/blood-2008-01-129783. Epub 2008 Jun 17.

  PMID: 18559976 RESULT

• McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013 Oct;2(5):662-73. doi: 10.1002/cam4.106. Epub 2013 Jul 21.

  PMID: 24403232 RESULT

• Ansell SM, Minnema MC, Johnson P, Timmerman JM, Armand P, Shipp MA, Rodig SJ, Ligon AH, Roemer MGM, Reddy N, Cohen JB, Assouline S, Poon M, Sharma M, Kato K, Samakoglu S, Sumbul A, Grigg A. Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study. J Clin Oncol. 2019 Feb 20;37(6):481-489. doi: 10.1200/JCO.18.00766. Epub 2019 Jan 8.

  PMID: 30620669 RESULT

• McCord R, Bolen CR, Koeppen H, Kadel EE 3rd, Oestergaard MZ, Nielsen T, Sehn LH, Venstrom JM. PD-L1 and tumor-associated macrophages in de novo DLBCL. Blood Adv. 2019 Feb 26;3(4):531-540. doi: 10.1182/bloodadvances.2018020602.

  PMID: 30770362 RESULT

• 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.

  PMID: 30975638 RESULT

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

sintilimab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisolone; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xiuhua Sun, Master

  The Second Affiliated Hospital of Dalian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiuhua Sun, Master

CONTACT

+8617709873631; sxh17709873631@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Model Details: 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.

Study Record Dates

• First Submitted: March 6, 2022
• First Posted: March 15, 2022
• Study Start: March 25, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 15, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share