Lymphoma, Large B-Cell, DiffusePhase 1/2NCT02737085
the Sequential Therapy of CD19-targeted and CD20-targeted CAR-T Cell Therapy for Diffuse Large B Cell Lymphoma(DLBCL)
A Phase 1/2 study testing Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells in people with Lymphoma, Large B-Cell, Diffuse, run by Southwest Hospital, China at 1 site in China.
Trial summary
The main purpose of this study is to explore the sequential therapeutic effect of CD19-targeted and CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Diffuse Large B Cell Lymphoma(DLBCL) Read more about this study
- Who is it for?
- Ages 14 to 75 years
- Conditions the study is for
- Lymphoma, Large B-Cell, Diffuse
- What is being tested?
- Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Mar 2016to Dec 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 14 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- CD19-expressing and CD20-expressing Diffuse Large B Cell Lymphoma(DLBCL) must be assured and must be relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
- Patients enrolled must have an evaluated score above 60 with KPS.
- Expected survival time of patients enrolled is over 3 months.
- Gender is not limited, age from 14 years to 75 years.
- Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
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- Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
- Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)
- Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy).
- Ability to give informed consent.
- Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
- Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
- Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
- Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
- Patients volunteer to participate in the research
Who cannot join
- Subjects meeting any of the following criteria are not eligible for participation in the study:
- Patients are evaluated below 50 scores with KPS.
- Evident signs suggesting that patients are potentially allergic to cytokines.
- Frequent infection history and recent infection is uncontrolled.
- Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
- Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
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- Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
- Pregnancy and nursing females. HIV infection.
- Active hepatitis B or active hepatitis C.
- Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
- Other situations we think not eligible for participation in the research.
Trial locations and contacts
1 site in 1 country.
China1 site
Southwest Hospital of Third Millitary Medical University
Chongqing, Chongqing Municipality, 400000
About this study
The main purpose of this study is to explore the sequential therapeutic effect of CD19-targeted and CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Diffuse Large B Cell Lymphoma(DLBCL)
Read the detailed description
The anti-CD20 antibody has been broadly used in the treatment of B cell malignancies and exhibited good clinical outcomes. The CD19-targeted CAR-T has shown excellent therapeutic efficiency in B cell malignancies,especially in acute lymphocytic leukemia. However, patients treated with CD19-targeted CAR-T may face relapse of CD19 mutation. Therefore we attempt to treat Diffuse Large B Cell Lymphoma(DLBCL) patients by sequential therapy of the 2 targets and hope to combine their advantages.
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Being tested
- Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells
- Keywords
- CD19-targeted CAR-T Cell, CD20-targeted CAR-T Cell, Diffuse Large B Cell Lymphoma
- 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.
Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cellsBiological
Also called CD19-targeted CAR-T cells and CD20-targeted CAR-T cells
Patients receive autologous-derived CD19-targeted CAR-T cells following CD20-targeted CAR-T cells after receiving lymphodepleting chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Diffuse Large B Cell Lymphoma(DLBCL) | Experimental | The trial will be conducted in a manner of simon two-stage design with Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with Diffuse Large B Cell Lymphoma(DLBCL). Only when the expected reaction rate is achieved the 30 patients left can be recruited. Receives: Biological: Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events That Are Related to Treatment
Determine the toxicity profile of the CD19-targeted and CD20-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
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 Lymphoma, Large B-Cell, DiffuseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southwest Hospital, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jieping Chen, Southwest Hospital, China
- Investigators
- Jieping Chen, MD,PhD, Principal investigator, Department of Hematology, Southwest Hospital, Third Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02737085
- Sponsor's protocol ID
- Southwest Hospital, China
- Status last verified
- Mar 2016
- First submitted
- 8 Apr 2016
- Last updated
- 7 Sep 2016
- 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 7 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- the Sequential Therapy of CD19-targeted and CD20-targeted CAR-T Cell Therapy for Diffuse Large B Cell Lymphoma(DLBCL)
- ClinicalTrials.gov ID
- NCT02737085
- Acronym / sponsor ID
- Southwest Hospital, China
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Keywords
- CD19-targeted CAR-T Cell, CD20-targeted CAR-T Cell, Diffuse Large B Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Southwest Hospital, ChinaUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 13 Apr 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 main purpose of this study is to explore the sequential therapeutic effect of CD19-targeted and CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of Diffuse Large B Cell Lymphoma(DLBCL)
Detailed description
The anti-CD20 antibody has been broadly used in the treatment of B cell malignancies and exhibited good clinical outcomes. The CD19-targeted CAR-T has shown excellent therapeutic efficiency in B cell malignancies,especially in acute lymphocytic leukemia. However, patients treated with CD19-targeted CAR-T may face relapse of CD19 mutation. Therefore we attempt to treat Diffuse Large B Cell Lymphoma(DLBCL) patients by sequential therapy of the 2 targets and hope to combine their advantages.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Diffuse Large B Cell Lymphoma(DLBCL) | Experimental | Biological: Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cellsThe trial will be conducted in a manner of simon two-stage design with Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with Diffuse Large B Cell Lymphoma(DLBCL). Only when the expected reaction rate is achieved the 30 patients left can be recruited. |
Who may qualify
- Ages
- 14 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- CD19-expressing and CD20-expressing Diffuse Large B Cell Lymphoma(DLBCL) must be assured and must be relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
- Patients enrolled must have an evaluated score above 60 with KPS.
- Expected survival time of patients enrolled is over 3 months.
- Gender is not limited, age from 14 years to 75 years.
- Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
Key exclusion criteria (13 listed)
- Subjects meeting any of the following criteria are not eligible for participation in the study:
- Patients are evaluated below 50 scores with KPS.
- Evident signs suggesting that patients are potentially allergic to cytokines.
- Frequent infection history and recent infection is uncontrolled.
- Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
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 |
|---|---|---|
| Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cellsAlso: CD19-targeted CAR-T cells and CD20-targeted CAR-T cellsPatients receive autologous-derived CD19-targeted CAR-T cells following CD20-targeted CAR-T cells after receiving lymphodepleting chemotherapy. | Biological | Diffuse Large B Cell Lymphoma(DLBCL) |
Primary outcome
Adverse Events That Are Related to Treatment
Time frame: 2 years
Determine the toxicity profile of the CD19-targeted and CD20-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2016.
- 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.
Jieping Chen, MD,PhD principal investigator
Department of Hematology, Southwest Hospital, Third Military 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 1/2 study testing Anti-CD19 CAR-T cells and Anti-CD20 CAR-T cells in people with Lymphoma, Large B-Cell, Diffuse, run by Southwest Hospital, China 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 15 inclusion and 13 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 7 Sep 2016. 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 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?
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?
Adverse Events That Are Related to Treatment (time frame: 2 years). 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 NCT02737085, 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 7 Sep 2016.