Primary Mediastinal Large B-cell LymphomaPhase 1/2NCT03346642
Two Stage Study of Combination of Chemotherapy, SHR-1210 and/or Decitabine for Relapsed/Refractory PMBCLs
A Phase 1/2 study testing Decitabine, GVD chemotherapy and SHR-1210 in people with Primary Mediastinal Large B-cell Lymphoma, run by Chinese PLA General Hospital at 2 sites in China.
Trial summary
This is a two stage, Phase I/II clinical trial for patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). In the first stage, the participants will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody (SHR-1210) treatment. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Primary Mediastinal Large B-cell Lymphoma
- What is being tested?
- Decitabine, GVD chemotherapy and SHR-1210
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesChina
- Study dates
- 1 May 2017to 1 Oct 2019
- Phase
- Phase 1/2
- 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
- All patients had histologically proven PMBCL, and Radiographically measureable disease.
- Eastern Cooperative Oncology Group performance status 0-2
- Disease recurring within 6 months after first-line chemotherapy or disease progression while receiving or persistent disease after first-line chemotherapy
- Bulky disease was defined as the presence of a mediastinal mass > 4.5 cm in axial diameter or extranodal lesion > 3 cm.
- Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
- Adequate organ function.
- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
- Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.
Who cannot join
- Known clinically active central nervous system involvement.
- Any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- Serious uncontrolled medical disorders or active infections, pulmonary infection especially
- Prior organ allograft.
- Receiving any other form of immunosuppressive medication, except steroid.
- Allogeneic hematopoietic stem cell transplantation within the last 5 years. 6） Known human immunodeficiency virus (HIV). 7） Has received a live vaccine within 30 days prior to first dose of study drug.
- 8） Women who are pregnant or breastfeeding.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Weidong Han, Doctor, 86-10-66937463, hanwdrsw@sina.com
Qingming Yang, Doctor, 86-10-55499341, yangqm@medmail.com.cn
- Recruiting
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Weidong Han, Doctor, 86-10-66937463, hanwdrsw@sina.com
Qingming Yang, Doctor, 86-10-55499341, yangqm@medmail.com.cn
About this study
Official title: Combined Chemotherapy and PD-1 Antibody(SHR-1210) With or Without Low-dose Decitabine Priming for Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL):Two Stage, Phase I/II Trail
This is a two stage, Phase I/II clinical trial for patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). In the first stage, the participants will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody (SHR-1210) treatment. The safety and efficacy of combined regimen will be evaluated. If deemed safe and efficacious, the investigators will proceed to the second stage of the study. In the second stage, the participants will receive GVD chemotherapy and SHR-1210 treatment with low-dose Decitabine priming. The safety and feasibility of combined regimens will be evaluated in phase I study. The feasibility will be accessed.
- Being tested
- Decitabine, GVD chemotherapy, SHR-1210
- Keywords
- Relapsed/Refractory, primary mediastinal large B-cell lymphoma, PD-1 antibody, Decitabine, GVD chemotherapy
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and histocompatibility leukocyte antigen (HLA) expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
GVD chemotherapyDrug
GVD regimen is a chemotherapy regimen consisted by Gemcitabine, Vinorelbine and Doxorubicine. Patients will be administrated with Gemcitabine 0.8 g/m2, Vinorelbine 30mg and Doxorubicin 20mg/m2 intravenously infusion.
SHR-1210Drug
Also called PD-1 antibody, PD-1 inhibitor
SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
| Study group | Role | What they receive |
|---|---|---|
| GVD and SHR-1210 with or without Decitabine | Experimental | This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed. Receives: Drug: Decitabine; Drug: GVD chemotherapy; Drug: SHR-1210 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects with treatment-related adverse events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Measured: Up to 120 days after last administration of SHR-1210
Objective response rate (ORR)
The antitumor efficacy of the combination treatments as measured by ORR was determined using the International Working Group 2007 criteria for malignant lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-586). Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment. ORR is defined as the sum of CR and PR.
Measured: Enrolled patients will be followed until death, withdrawal from study, or until 2 years.
Secondary outcomes (3)
Complete response (CR) rate
The CR rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Measured: Up to 2 years after completion of study treatment
Median progression-free survival (PFS) time
PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined using the International Working Group 2007 criteria for malignant lymphoma.
Measured: Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.
Median overall survival (OS) time
OS time was measured from the study entry to the date of death.
Measured: Patients will be followed until death, withdrawal from study, or until 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start1 May 2017
- Primary completion1 Mar 2019 (estimated)
- Study completion1 Oct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Mediastinal Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346642
- Sponsor's protocol ID
- CHN-PLAGH-BT-025
- Status last verified
- Nov 2018
- First submitted
- 7 Oct 2017
- Last updated
- 3 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Chemotherapy and PD-1 Antibody(SHR-1210) With or Without Low-dose Decitabine Priming for Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL):Two Stage, Phase I/II Trail
- ClinicalTrials.gov ID
- NCT03346642
- Acronym / sponsor ID
- CHN-PLAGH-BT-025
- Keywords
- Relapsed/Refractory, primary mediastinal large B-cell lymphoma, PD-1 antibody, Decitabine, GVD chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 1 Mar 2019 (estimated)
- Study completion
- 1 Oct 2019 (estimated)
- First posted
- 17 Nov 2017 (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 is a two stage, Phase I/II clinical trial for patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL). In the first stage, the participants will receive GVD (Gemcitabine, Vinorelbine and Doxorubicine) chemotherapy and PD-1 antibody (SHR-1210) treatment. The safety and efficacy of combined regimen will be evaluated. If deemed safe and efficacious, the investigators will proceed to the second stage of the study. In the second stage, the participants will receive GVD chemotherapy and SHR-1210 treatment with low-dose Decitabine priming. The safety and feasibility of combined regimens will be evaluated in phase I study. The feasibility will be accessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GVD and SHR-1210 with or without Decitabine | Experimental | Drug: Decitabine, Drug: GVD chemotherapy, Drug: SHR-1210This is a two stage study. For the first stage, the participants will receive the combination of GVD chemotherapy and PD-1 antibody SHR-1210. The patients enrolled into the second stage will received the combination of GVD and SHR-1210 with low-dose decitabine primed. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- All patients had histologically proven PMBCL, and Radiographically measureable disease.
- Eastern Cooperative Oncology Group performance status 0-2
- Disease recurring within 6 months after first-line chemotherapy or disease progression while receiving or persistent disease after first-line chemotherapy
- Bulky disease was defined as the presence of a mediastinal mass > 4.5 cm in axial diameter or extranodal lesion > 3 cm.
- Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
Key exclusion criteria (7 listed)
- Known clinically active central nervous system involvement.
- Any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- Serious uncontrolled medical disorders or active infections, pulmonary infection especially
- Prior organ allograft.
- Receiving any other form of immunosuppressive medication, except steroid.
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 |
|---|---|---|
| DecitabineDecitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and histocompatibility leukocyte antigen (HLA) expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function. | Drug | GVD and SHR-1210 with or without Decitabine |
| GVD chemotherapyGVD regimen is a chemotherapy regimen consisted by Gemcitabine, Vinorelbine and Doxorubicine. Patients will be administrated with Gemcitabine 0.8 g/m2, Vinorelbine 30mg and Doxorubicin 20mg/m2 intravenously infusion. | Drug | GVD and SHR-1210 with or without Decitabine |
| SHR-1210Also: PD-1 antibody, PD-1 inhibitorSHR-1210 is a humanized anti-PD-1 monoclonal antibody. | Drug | GVD and SHR-1210 with or without Decitabine |
Primary outcome
Number of Subjects with treatment-related adverse events (AEs)
Time frame: Up to 120 days after last administration of SHR-1210
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.
Objective response rate (ORR)
Time frame: Enrolled patients will be followed until death, withdrawal from study, or until 2 years.
The antitumor efficacy of the combination treatments as measured by ORR was determined using the International Working Group 2007 criteria for malignant lymphoma (J Clin Oncol. 2007 Feb 10;25(5):579-586). Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment. ORR is defined as the sum of CR and PR.
3 secondary outcomes
Complete response (CR) rate
Time frame: Up to 2 years after completion of study treatment
Median progression-free survival (PFS) time
Time frame: Patients will be followed until disease progression, death, withdrawal from study, or until 2 years.
Median overall survival (OS) time
Time frame: Patients will be followed until death, withdrawal from study, or until 2 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2018.
Related trials for Primary Mediastinal Large B-cell Lymphoma
Active, not recruitingPhase 3
Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
Primary Mediastinal Large B-Cell Lymphoma
Active, not recruitingPhase 1/2
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
DLBCL, High-grade B-cell Lymphoma (HGBCL)
Active, not recruitingPhase 1/2
Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma
Active, not recruitingPhase 1
Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL.
Grade 3b Follicular Lymphoma, Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between DLBCL and Classic HL
RecruitingPhase 2
Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL
Large B-cell Lymphoma
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.
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
Beijing, China
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, China
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Decitabine, GVD chemotherapy and SHR-1210 in people with Primary Mediastinal Large B-cell Lymphoma, run by Chinese PLA General Hospital at 2 sites 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 8 inclusion and 7 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 3 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects with treatment-related adverse events (AEs) (time frame: Up to 120 days after last administration of SHR-1210). The study lists 2 primary outcomes in all. 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 3 Dec 2018.