Diffuse Large B-Cell LymphomaPhase 2NCT05280626
First-line Treatment of P53 Mutation With PD-L1 Expression in DLBCL With Anti-PD-1 Mab and R-CHOP
A Phase 2 study testing Sintilimab and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by Innovent Biologics (Suzhou) Co. Ltd..
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Sintilimab and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 25 Mar 2022to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
Read the 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.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Sintilimab, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SintilimabDrug
Also called Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone
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.
RituximabDrug
Also called Cyclophosphamide, Doxorubicin, Oncovin, Prednisolone
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRR
To assess complete response rate (CRR)
Measured: 1 year
Secondary outcomes (3)
PFS
Defined as the time from the beginning of treatment to the first imaging disease progression or death (whichever occurs first).
Measured: 1 year
ORR
Objective response rate (ORR)
Measured: 1 year
OS
Defined as the time from the start of treatment to the death of the subject due to any cause.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start25 Mar 2022 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Innovent Biologics (Suzhou) Co. Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Innovent Biologics (Suzhou) Co. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Principal investigator, sunxiuhua, Innovent Biologics (Suzhou) Co. Ltd.
- Investigators
- Xiuhua Sun, Master, Principal investigator, The Second Affiliated Hospital of Dalian Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05280626
- Sponsor's protocol ID
- CIBI308Y047
- Status last verified
- Mar 2022
- First submitted
- 6 Mar 2022
- Last updated
- 15 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 20548096Young 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.
PubMed 18559976McDermott 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.
PubMed 24403232Ansell 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.
PubMed 30620669McCord 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.
PubMed 30770362Pascual 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.
PubMed 30975638
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05280626
- Acronym / sponsor ID
- CIBI308Y047
- Conditions
- Diffuse Large B-Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Innovent Biologics (Suzhou) Co. Ltd.Industry (pharma, biotech, devices)
- Study start
- 25 Mar 2022 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| A: PD-1+R-CHOP | Experimental | Drug: Sintilimab, Drug: RituximabAfter 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. |
| B: R-CHOP | Active comparator | Drug: RituximabAfter 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SintilimabAlso: Cyclophosphamide, Doxorubicin, Oncovin, PrednisoloneAfter 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. | Drug | A: PD-1+R-CHOP |
| RituximabAlso: Cyclophosphamide, Doxorubicin, Oncovin, PrednisoloneAfter 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. | Drug | A: PD-1+R-CHOP, B: R-CHOP |
Primary outcome
CRR
Time frame: 1 year
To assess complete response rate (CRR)
3 secondary outcomes
PFS
Time frame: 1 year
ORR
Time frame: 1 year
OS
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
- Results publication: PubMed 20548096Coiffier 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.
- Results publication: PubMed 18559976Young 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.
- Results publication: PubMed 24403232McDermott 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.
- Results publication: PubMed 30620669Ansell 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.
- Results publication: PubMed 30770362McCord 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.
- Results publication: PubMed 30975638Pascual 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xiuhua Sun, Master principal investigator
The Second Affiliated Hospital of Dalian Medical University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sintilimab and Rituximab in people with Diffuse Large B-Cell Lymphoma, run by Innovent Biologics (Suzhou) Co. Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiuhua Sun, Master (+8617709873631, sxh17709873631@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRR (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05280626, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.