Refractory Diffuse Large B-Cell LymphomaPhase 1C-CAR011NCT02976857
A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects
A Phase 1 study testing C-CAR-011 in people with Refractory Diffuse Large B-Cell Lymphoma, run by Shanghai AbelZeta Ltd. at 1 site in China.
Trial summary
The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- C-CAR-011
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- Dec 2016to 9 Jan 2019
- Phase
- Phase 1
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016)
- Refractory DLBCL
- All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3)
- At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm)
- Age 18-70 years old, male or female
- Expected survival ≥ 12 weeks
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- ECOG score 0-1
- Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of pericardial effusion as determined by an ECHO
- At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments)
- No contraindications of peripheral blood apheresis
- Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial measures
- Volunteered to participate in this study and signed informed consent
Who cannot join
- Have a history of allergy to cellular products
- Used any genetically modified T cell therapy
- History of allogeneic hematopoietic stem cell transplantation
- Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons
- Patients with class III and IV heart failure according to the NYHA Heart Failure Classifications
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- A history of QT prolongation
- A history of epilepsy or other central nervous system disorders
- The patient had a history of other primary cancers, with the following exceptions: Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ carcinoma such as cervical cancer, bladder cancer or breast cancer
- Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
- Used of systemic steroids within two weeks (using inhaled steroids is an exception)
- Women who are pregnant or lactating or have breeding intent in 6 months
- Participated in any other clinical trial within three months
- The investigators believe that any increase in the risk of the subject or interference with the results of the trial
Trial locations and contacts
1 site in 1 country.
China1 site
Hematological Department, People's Hospital of Jiangsu Province
Nanjing, Jiangsu, 210029
About this study
Official title: A Phase 1 Single Center, Non-randomized Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Refractory Diffuse Large B-cell Lymphoma
The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL
Read the detailed description
The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose group as below:
Dose CAR+ cells/kg
Low 0.8×106
Medium 2.5×106
High 5.0×106
DLT is evaluated within 30 days post C-CAR011 infusion).
- Conditions
- Refractory Diffuse Large B-Cell Lymphoma
- Being tested
- C-CAR-011
- Keywords
- refractory diffuse large B-cell lymphoma, anti-CD19 chimeric antigen receptor T-cell
- 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.
C-CAR-011Biological
Also called CAR-CD19
lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene.
| Study group | Role | What they receive |
|---|---|---|
| C-CAR011 | Experimental | C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion. Receives: Biological: C-CAR-011 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.
Measured: 28 days
Secondary outcomes (2)
Overall response rate
Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria.
Measured: 4 and 12 weeks
Disease control rate
Disease control rate (DCR） = complete response (CR) rate + partial response (PR) rate + stable disease (SD) rate, DCR will be assessed at weeks 12 according to International Working Group (IWG) revised criteria.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2016 (estimated)
- Study startDec 2016
- Primary completion11 Sep 2018
- Study completion9 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai AbelZeta Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jianyong Li, Principal investigator, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02976857
- Sponsor's protocol ID
- CBMG2016002
- Acronym
- C-CAR011
- Status last verified
- Nov 2016
- First submitted
- 21 Nov 2016
- Last updated
- 17 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Single Center, Non-randomized Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Refractory Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT02976857
- Acronym / sponsor ID
- C-CAR011 / CBMG2016002
- Conditions
- Refractory Diffuse Large B-Cell Lymphoma
- Keywords
- refractory diffuse large B-cell lymphoma, anti-CD19 chimeric antigen receptor T-cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Shanghai AbelZeta Ltd.Industry (pharma, biotech, devices)
- Collaborators
- The First Affiliated Hospital with Nanjing Medical University
- Study start
- Dec 2016
- Primary completion
- 11 Sep 2018 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 29 Nov 2016 (estimated)
- 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.
The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL
Detailed description
The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose group as below:
Dose CAR+ cells/kg
Low 0.8×106
Medium 2.5×106
High 5.0×106
DLT is evaluated within 30 days post C-CAR011 infusion).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| C-CAR011 | Experimental | Biological: C-CAR-011C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016)
- Refractory DLBCL
- All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3)
- At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm)
- Age 18-70 years old, male or female
Key exclusion criteria (14 listed)
- Have a history of allergy to cellular products
- Used any genetically modified T cell therapy
- History of allogeneic hematopoietic stem cell transplantation
- Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons
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 |
|---|---|---|
| C-CAR-011Also: CAR-CD19lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene. | Biological | C-CAR011 |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: 28 days
Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.
2 secondary outcomes
Overall response rate
Time frame: 4 and 12 weeks
Disease control rate
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2019.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Jianyong Li principal investigator
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing C-CAR-011 in people with Refractory Diffuse Large B-Cell Lymphoma, run by Shanghai AbelZeta Ltd. 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 12 inclusion and 14 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: finished, as of the sponsor's last update on 17 Jan 2019. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: 28 days). 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 NCT02976857, which also lists 1 linked publication.
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 17 Jan 2019.