Diffuse Large B Cell LymphomaPhase 2NCT04659434
Sintilimab Plus R-GemOx as Second-line Salvage Therapy in Patients With R/R DLBCL
A Phase 2 study testing Sintilimab in people with Diffuse Large B Cell Lymphoma and Relapsed Diffuse Large B-Cell Lymphoma, run by Qian Wenbin at 1 site in China.
Trial summary
This study evaluates the addition of Sintilimab to current 2nd line salvage therapy of Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL). All patients will receive four cycles of sintilimab plus R-GemOx. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Sintilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteChina
- Study dates
- 10 Dec 2020to 10 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Willingness to provide written informed consent.
- Age range from 18 to 80 years;
- Pathologically confirmed CD20+ diffuse large B-cell lymphoma
- According to Lugano 2014, at least one measurable nodular lesion with a length of greater than 15 mm, or extranodal lesion greater than 10 mm, lesion on FDG-PET scan demonstrates uptake);
- Diffuse large B-cell lymphoma patients failed to first-line rituximab based chemotherapy including anthracycline or anthracycline
- Patients are allowed to receive palliative radiotherapy, but the last time radiotherapy cannot be within 7 days before the first study drug administration;
Show all 9Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- Adequate organ function
- Expectation survival time over 3 months;
Who cannot join
- History of other malignancy within the past 5 years (except for 1. basal cell carcinoma of the skin and 2. carcinoma in situ of the cervix and 3. patients who had received treatment for the purpose of cure and had not developed a malignant tumor with a known active disease in the previous 5 years);
- Patients who had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of the enrollment (if patients received small-molecule targeted drug therapy, they could be included in the study if the drug was discontinued for more than 5 half-lives), or had not recovered from the previous toxicity;
- Previous treatment with anti-PD-1 antibody, anti-PD-L1 antibody or other medications that stimulates or collaboratively inhibits T cell receptors
- Patients previously received anti-CD20 antibody combined GemOx regimen;
- Evidence of central nervous system invasion;
- Patients received systemic treatment of traditional Chinese herb with anti-tumor indications or immunomodulatory drugs (including thyroxin, interferon and interleukinin, except for local use to control pleural effusions) within 2 weeks before first administration;
Show all 25Show fewer
- Patients with autoimmune diseases requiring treatment or with a history of syndrome requiring systemic use of steroid immunosuppressive agents, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc;
- Patients received systemic glucocorticoid therapy (excluding nasal spray, inhaled or other topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to the first administration;
- Clinically uncontrollable pleural effusion/peritoneal effusion (patients who do not need drainage effusion or do not significantly increase the effusion after 3 days of drainage can be enrolled);
- Patients who have had previous organ transplants (except autologous hematopoietic stem cell transplants);
- Patients are allergic to sintilimab, CD20 monoclonal antibody and GemOx regimen
- Patients has not fully recovered from toxicity and/or complications due to any intervention prior to initiation of treatment (i.e., ≤ grade 1 or baseline, excluding fatigue or hair loss);
- A confirmed history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive);
- A confirmed history of Novel Coronavirus infection;
- Patients with hepatitis B (HBV HBsAg positive and HBV-DNA≥105), hepatitis C (HCV) infection (HCV antibody positive and HCV-RNA detectable); And subjects with other acquired or congenital immune deficiency diseases, including but not limited to hiv-infected;
- Patients who received the live vaccine within 4 weeks of the start of the enrollment;
- Pregnant or lactating women;
- Patients who have received grade II or above surgery within 3 weeks before enrollment;
- Patients with significant coagulation abnormality;
- Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interfere with results interpretation, including uncontrolled diabetes, or pulmonary disease (a history of interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchospasm);
- Patients who received the live vaccine within 4 weeks of the start of the enrollment;
- Severe or uncontrolled infections;
- Patients with history of severe neurological or psychiatric illness, including dementia or epilepsy;
- Patients with drug abuse, medical, psychological or social conditions that may interfere with the study results or the assessment of the study results;
- Patients are unsuitable for the enrollment according to investigator's judgement.
Trial locations and contacts
1 site in 1 country.
hui Liu contact
China1 site
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
About this study
Official title: A Phase II Study of Anti-PD-1 Antibody (Sintilimab) Plus Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) as Second-line Salvage Therapy in Patients With Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)
This study evaluates the addition of Sintilimab to current 2nd line salvage therapy of Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL). All patients will receive four cycles of sintilimab plus R-GemOx. Afterwards, 1) patients who achieve CR assessed by PET-CT and are eligible for autologous stem cell transplantation (ASCT) will undergo ASCT. After transplantation, patients will receive sintilimab monotherapy up to 8 cycles or until disease recurrence and progression, death, intolerance and toxicity, withdrawal of informed consent, or other reasons specified in the protocol. 2) Patients who achieve CR assessed by PET-CT and are not eligible for ASCT will directly receive sintilimab monotherapy as maintenance treatment for a maximum of 8 cycles as described above. 3) Patients achieved PR, SD or PD assessed by PET/CT will withdraw from this study and receive proper treatment based on investigator's decision.
Read the detailed description
Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. The R-GemOx regimen has been adopted by numerous medical institutions internationally as therapy for older patients or comorbid patients with relapsed or refractory DLBCL and as a back-bone for the investigation of novel therapies in combination with chemotherapy. The cytotoxic T-lymphocyte co-receptor PD-1 has been extensively studied and is recognized to provide critical inhibitory signals that down-regulate T-cell function and provides a mechanism for immune evasion for tumors. PD-L1, the ligand of PD-1 is expressed on DLBCL tumor cells, along with infiltrating non-malignant cells, primarily macrophages, with PD-1 expressed on tumor infiltrating lymphocytes (TILs). Sintilimab targets programmed PD-1 on tumor cells and prevents interaction with either PD-1 receptor or B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells. Interference of the PD-L1:PD-1 and PDL1:B7.1 interactions may enhance the magnitude and quality of the tumor-specific T-cell response through increased T-cell priming, expansion, and/or effector function. This study of sintilimab in combination with rituximab, gemcitabine and oxaliplatin aims to address the unmet clinical need of patients with relapsed and refractory DLBCL. It is based upon a sound mechanistic approach, investigating the activity of novel agents and will aim to compressively explore biomarkers of response. The primary objective will be the complete response rate (CRR) of this salvage therapy. A maintenance phase of sintilimab will be added as this may induce an on-going T-cell response to neo-antigens released as a result of previous treatment.
- Conditions
- Diffuse Large B Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- Being tested
- Sintilimab
- 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 IBI308
Patients receive sintiliman+R-GemOx three weeks for a cycle, detailed as follows:
Combination therapy
- Anti-PD-1 antibody (sintilimab): Fixed dose of 200 mg every 3 weeks, d0, intravenous drip (without pretreatment), infusion time: 30 mintutes (no less than 20 mins, no more than 60 mins), for 4 cycles
- R-GemOx: Rituximab 375mg/m2, d1; Gemcitabine 1000mg, d2; Oxaliplatin 100mg/m2, d2; every 3 weeks for a cycle, 4 cycle as protocol specified.
Monotherapy:
-Anti-PD-1 antibody (sintilimab): Fixed dose of 200 mg every 3 weeks, d0, intravenous drip (without pretreatment), infusion time: 30 mintutes (no less than 20 mins, no more than 60 mins), for 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| treatment group | Experimental | Sintilimab 200mg ivdrip Q3W; Rituximab 375mg/m2 ivdrip; Gemcitabine 1000mg ivdrip; Oxaliplatin 100mg/m2 ivdrip Receives: Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
Complete response rate after treated by Sintilimab and R-GemOx
Measured: 6 weeks after the last dose of the combination therapy (each cycle is 21 days)
Secondary outcomes (3)
Over response rate (ORR)
Overall response rate after treated by Sintilimab and R-GemOx
Measured: 6 weeks after the last dose of the combination therapy (each cycle is 21 days)
Overall Survival (OS)
from date of inclusion to date of progression, relapse, or death from any cause
Measured: 2 years
Rate of grade 3 or 4 treatment related adverse effect
All the adverse events of the patients related will be assessed and graded by NCI CTCAE v 5.0
Measured: Time Frame: Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of anti-PD-1 antibody (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start10 Dec 2020 (estimated)
- Primary completion10 Dec 2022 (estimated)
- Study completion10 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qian Wenbin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Qian Wenbin, Second Affiliated Hospital, Zhejiang University, School of Medicine
- Investigators
- wenbin Qian, Principal investigator, 2nd Affiliated Hospital, School of Medicine, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04659434
- Sponsor's protocol ID
- IR2020001398
- Status last verified
- Dec 2020
- First submitted
- 26 Nov 2020
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Anti-PD-1 Antibody (Sintilimab) Plus Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) as Second-line Salvage Therapy in Patients With Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT04659434
- Acronym / sponsor ID
- IR2020001398
- Conditions
- Diffuse Large B Cell Lymphoma, Relapsed Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Qian WenbinUniversity, hospital or other
- Study start
- 10 Dec 2020 (estimated)
- Primary completion
- 10 Dec 2022 (estimated)
- Study completion
- 10 Dec 2025 (estimated)
- First posted
- 9 Dec 2020 (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.
This study evaluates the addition of Sintilimab to current 2nd line salvage therapy of Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) for patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL). All patients will receive four cycles of sintilimab plus R-GemOx. Afterwards, 1) patients who achieve CR assessed by PET-CT and are eligible for autologous stem cell transplantation (ASCT) will undergo ASCT. After transplantation, patients will receive sintilimab monotherapy up to 8 cycles or until disease recurrence and progression, death, intolerance and toxicity, withdrawal of informed consent, or other reasons specified in the protocol. 2) Patients who achieve CR assessed by PET-CT and are not eligible for ASCT will directly receive sintilimab monotherapy as maintenance treatment for a maximum of 8 cycles as described above. 3) Patients achieved PR, SD or PD assessed by PET/CT will withdraw from this study and receive proper treatment based on investigator's decision.
Detailed description
Rituximab is a chimeric mouse/human monoclonal antibody that binds to CD20, on pre-B and mature B lymphocytes and eliminates these cells potentially via a number of different mechanisms. The R-GemOx regimen has been adopted by numerous medical institutions internationally as therapy for older patients or comorbid patients with relapsed or refractory DLBCL and as a back-bone for the investigation of novel therapies in combination with chemotherapy. The cytotoxic T-lymphocyte co-receptor PD-1 has been extensively studied and is recognized to provide critical inhibitory signals that down-regulate T-cell function and provides a mechanism for immune evasion for tumors. PD-L1, the ligand of PD-1 is expressed on DLBCL tumor cells, along with infiltrating non-malignant cells, primarily macrophages, with PD-1 expressed on tumor infiltrating lymphocytes (TILs). Sintilimab targets programmed PD-1 on tumor cells and prevents interaction with either PD-1 receptor or B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells. Interference of the PD-L1:PD-1 and PDL1:B7.1 interactions may enhance the magnitude and quality of the tumor-specific T-cell response through increased T-cell priming, expansion, and/or effector function. This study of sintilimab in combination with rituximab, gemcitabine and oxaliplatin aims to address the unmet clinical need of patients with relapsed and refractory DLBCL. It is based upon a sound mechanistic approach, investigating the activity of novel agents and will aim to compressively explore biomarkers of response. The primary objective will be the complete response rate (CRR) of this salvage therapy. A maintenance phase of sintilimab will be added as this may induce an on-going T-cell response to neo-antigens released as a result of previous treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment group | Experimental | Drug: SintilimabSintilimab 200mg ivdrip Q3W; Rituximab 375mg/m2 ivdrip; Gemcitabine 1000mg ivdrip; Oxaliplatin 100mg/m2 ivdrip |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Willingness to provide written informed consent.
- Age range from 18 to 80 years;
- Pathologically confirmed CD20+ diffuse large B-cell lymphoma
- According to Lugano 2014, at least one measurable nodular lesion with a length of greater than 15 mm, or extranodal lesion greater than 10 mm, lesion on FDG-PET scan demonstrates uptake);
- Diffuse large B-cell lymphoma patients failed to first-line rituximab based chemotherapy including anthracycline or anthracycline
Key exclusion criteria (25 listed)
- History of other malignancy within the past 5 years (except for 1. basal cell carcinoma of the skin and 2. carcinoma in situ of the cervix and 3. patients who had received treatment for the purpose of cure and had not developed a malignant tumor with a known active disease in the previous 5 years);
- Patients who had received other antitumor therapy (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks before the start of the enrollment (if patients received small-molecule targeted drug therapy, they could be included in the study if the drug was discontinued for more than 5 half-lives), or had not recovered from the previous toxicity;
- Previous treatment with anti-PD-1 antibody, anti-PD-L1 antibody or other medications that stimulates or collaboratively inhibits T cell receptors
- Patients previously received anti-CD20 antibody combined GemOx regimen;
- Evidence of central nervous system invasion;
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: IBI308Patients receive sintiliman+R-GemOx three weeks for a cycle, detailed as follows: Combination therapy * Anti-PD-1 antibody (sintilimab): Fixed dose of 200 mg every 3 weeks, d0, intravenous drip (without pretreatment), infusion time: 30 mintutes (no less than 20 mins, no more than 60 mins), for 4 cycles * R-GemOx: Rituximab 375mg/m2, d1; Gemcitabine 1000mg, d2; Oxaliplatin 100mg/m2, d2; every 3 weeks for a cycle, 4 cycle as protocol specified. Monotherapy: -Anti-PD-1 antibody (sintilimab): Fixed dose of 200 mg every 3 weeks, d0, intravenous drip (without pretreatment), infusion time: 30 mintutes (no less than 20 mins, no more than 60 mins), for 8 cycles | Drug | treatment group |
Primary outcome
Complete response rate
Time frame: 6 weeks after the last dose of the combination therapy (each cycle is 21 days)
Complete response rate after treated by Sintilimab and R-GemOx
3 secondary outcomes
Over response rate (ORR)
Time frame: 6 weeks after the last dose of the combination therapy (each cycle is 21 days)
Overall Survival (OS)
Time frame: 2 years
Rate of grade 3 or 4 treatment related adverse effect
Time frame: Time Frame: Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of anti-PD-1 antibody (each cycle is 28 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Individual participant dataSharing planned: No
Related trials for Diffuse Large B Cell Lymphoma
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
RecruitingPhase 2
Safety and Efficacy of Epcoritamab With Gemcitabine, Dexamethasone, and Cisplatin (GDP) Salvage Chemotherapy in Relapsed Refractory Large B-cell Lymphoma
Large Cell Lymphoma, Diffuse, Relapsed Cancer
RecruitingObservational study
An Observational Study of Glofitamab in Chinese Adult Participants With 2L Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
RecruitingPhase 1
AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")
AIDS-Related Diffuse Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
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. This study is not recruiting at the moment.
hui Liu contact
wenbin Qian principal investigator
2nd Affiliated Hospital, School of Medicine, Zhejiang University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sintilimab in people with Diffuse Large B Cell Lymphoma and Relapsed Diffuse Large B-Cell Lymphoma, run by Qian Wenbin at 1 site in China.
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 9 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact wenbin Qian (13605801032, qianwb@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response rate (time frame: 6 weeks after the last dose of the combination therapy (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Dec 2020; AzTrials last refreshed its copy on 6 Nov 2026.