Recurrent or Refractory B Cell MalignancyPhase 1/2NCT03207178
Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma
A Phase 1/2 study testing Mixed CD19/CD20 CAR-T Transfer in people with Recurrent or Refractory B Cell Malignancy, run by Shanghai Longyao Biotechnology Inc., Ltd. at 1 site in China.
Trial summary
Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Recurrent or Refractory B Cell Malignancy
- What is being tested?
- Mixed CD19/CD20 CAR-T Transfer
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2017to 28 Feb 2020
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 Years to 70 Years, Male and female
- Survival time>12 weeks
- B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory tests and imaging tests
- Chemotherapy failure or recurrent B cell lymphomas
- Creatinine< 2.5mg/dl
- Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level
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- Bilirubin<2.0mg/dl
- Karnofsky Performance Status>50% at the time of screening
- Adequate pulmonary, renal, hepatic, and cardiac function
- Fail in autologous or allogenic haemopoietic stem cell transplantation
- Free of leukocytes removal contraindications
- Voluntarily join CAR-T clinical trial
- Understand and sign written informed consent
Who cannot join
- Pregnant or nursing women or women with pregnancy plan in half a year
- Any infectious disease (HIV, active tuberculosis, ect.)
- Active hepatitis B, active hepatitis C infection
- Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte amplification is below 5 fold with the costimulation of cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8)
- Abnormal vital signs or cannot cooperate with the inspectors
- mental or psychological disease cannot cooperate with treatment and curative effect evaluation
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- Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2(IL-2)
- General infection or local severe infection, or other infection that is not controlled
- Dysfunction in lung, heart, kidney and brain
- Severe autoimmune diseases
- Other symptoms that are not applicable for CAR-T
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Longyao Biotechnology Inc., Ltd.
Shanghai, Jingan, 200072
Wang Xin, M.D., 185-1602-2625 ext. +86, wangxin928@163.com
About this study
Official title: Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma
Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.
Read the detailed description
To determine:
Primary Outcome Measure:
The Overall complete remission rate and one-year survival rate of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell lymphomas.
The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments.
Secondary Outcome Measures:
Evaluate the initial effect time, time to disease progression, and life quality improvement of combination transfer compare to single target treatments.
Evaluate the safety and tolerability of combination transfer compare to single target treatments by observation of high fever duration in patients and testing related cell factor level in peripheral blood.
- Being tested
- Mixed CD19/CD20 CAR-T Transfer
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mixed CD19/CD20 CAR-T TransferBiological
Autologous CD19 CAR-T cells and CD20 CAR-T cells with average 1-5*10^6 cells/kg body weight,separately.
| Study group | Role | What they receive |
|---|---|---|
| Mixed CD19/CD20 CAR-T Transfer | Experimental | Subjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts Receives: Biological: Mixed CD19/CD20 CAR-T Transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall complete remission rate
The complete remission rate will be evaluated by routine methods.
Measured: Half a year
Secondary outcomes (6)
The initial effect time
The initial effect time will be recorded.
Measured: 1 year
The one-year survival rate
The one-year survival rate will be recorded.
Measured: 1 year
The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Measured: 1 month
The time to disease progression
The time to disease progression will be counted after complete remission.
Measured: 1 year
The one-year recurrence
The one-year recurrence will be counted after complete remission.
Measured: 1 year
The life quality improvement
The life quality improvement will be evaluated by appetite,sleep,pain and mental state.
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 posted2 Jul 2017
- Study start1 Mar 2017
- Primary completion28 Feb 2019 (estimated)
- Study completion28 Feb 2020 (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 Recurrent or Refractory B Cell MalignancyStudies 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Longyao Biotechnology Inc., Ltd.
- Sponsor type
- University, hospital or other
- Collaborators
- Xuzhou Medical University, Shanghai Jiao Tong University School of Medicine
- Responsible party
- Sponsor
- Investigators
- Shengqin Ye, M.D., Principal investigator, Shanghai Longyao Biotechnology Inc., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03207178
- Sponsor's protocol ID
- LYCT-1701
- Status last verified
- Jun 2017
- First submitted
- 23 Jun 2017
- Last updated
- 2 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.
PubMed 25444722Witkowska M, Smolewski P. Emerging immunotherapy and strategies directly targeting B cells for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 2015;7(1):37-46. doi: 10.2217/imt.14.93.
PubMed 25572478Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, Feldman SA, Iwamoto AT, Kurlander R, Maric I, Goy A, Hansen BG, Wilder JS, Blacklock-Schuver B, Hakim FT, Rosenberg SA, Gress RE, Kochenderfer JN. Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. J Clin Oncol. 2016 Apr 1;34(10):1112-21. doi: 10.1200/JCO.2015.64.5929. Epub 2016 Jan 25.
PubMed 26811520Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs. 2017 Mar;77(3):237-245. doi: 10.1007/s40265-017-0690-8.
PubMed 28110394Ernst 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 34515338Sang W, Shi M, Yang J, Cao J, Xu L, Yan D, Yao M, Liu H, Li W, Zhang B, Sun K, Song X, Sun C, Jiao J, Qin Y, Sang T, Ma Y, Wu M, Gao X, Cheng H, Yan Z, Li D, Sun H, Zhu F, Wang Y, Zeng L, Li Z, Zheng J, Xu K. Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Cancer Med. 2020 Aug;9(16):5827-5838. doi: 10.1002/cam4.3259. Epub 2020 Jul 1.
PubMed 32608579
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT03207178
- Acronym / sponsor ID
- LYCT-1701
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shanghai Longyao Biotechnology Inc., Ltd.University, hospital or other
- Collaborators
- Xuzhou Medical University, Shanghai Jiao Tong University School of Medicine
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 28 Feb 2019 (estimated)
- Study completion
- 28 Feb 2020 (estimated)
- First posted
- 2 Jul 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.
Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.
Detailed description
To determine:
Primary Outcome Measure:
The Overall complete remission rate and one-year survival rate of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell lymphomas.
The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments.
Secondary Outcome Measures:
Evaluate the initial effect time, time to disease progression, and life quality improvement of combination transfer compare to single target treatments.
Evaluate the safety and tolerability of combination transfer compare to single target treatments by observation of high fever duration in patients and testing related cell factor level in peripheral blood.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mixed CD19/CD20 CAR-T Transfer | Experimental | Biological: Mixed CD19/CD20 CAR-T TransferSubjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 18 Years to 70 Years, Male and female
- Survival time>12 weeks
- B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory tests and imaging tests
- Chemotherapy failure or recurrent B cell lymphomas
- Creatinine< 2.5mg/dl
Key exclusion criteria (11 listed)
- Pregnant or nursing women or women with pregnancy plan in half a year
- Any infectious disease (HIV, active tuberculosis, ect.)
- Active hepatitis B, active hepatitis C infection
- Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte amplification is below 5 fold with the costimulation of cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8)
- Abnormal vital signs or cannot cooperate with the inspectors
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 |
|---|---|---|
| Mixed CD19/CD20 CAR-T TransferAutologous CD19 CAR-T cells and CD20 CAR-T cells with average 1-5*10^6 cells/kg body weight,separately. | Biological | Mixed CD19/CD20 CAR-T Transfer |
Primary outcome
Overall complete remission rate
Time frame: Half a year
The complete remission rate will be evaluated by routine methods.
6 secondary outcomes
The initial effect time
Time frame: 1 year
The one-year survival rate
Time frame: 1 year
The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity)
Time frame: 1 month
The time to disease progression
Time frame: 1 year
The one-year recurrence
Time frame: 1 year
The life quality improvement
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 25444722Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.
- Background: PubMed 25572478Witkowska M, Smolewski P. Emerging immunotherapy and strategies directly targeting B cells for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 2015;7(1):37-46. doi: 10.2217/imt.14.93.
- Background: PubMed 26811520Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, Feldman SA, Iwamoto AT, Kurlander R, Maric I, Goy A, Hansen BG, Wilder JS, Blacklock-Schuver B, Hakim FT, Rosenberg SA, Gress RE, Kochenderfer JN. Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. J Clin Oncol. 2016 Apr 1;34(10):1112-21. doi: 10.1200/JCO.2015.64.5929. Epub 2016 Jan 25.
- Background: PubMed 28110394Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs. 2017 Mar;77(3):237-245. doi: 10.1007/s40265-017-0690-8.
- 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.
- Derived from this study: PubMed 32608579Sang W, Shi M, Yang J, Cao J, Xu L, Yan D, Yao M, Liu H, Li W, Zhang B, Sun K, Song X, Sun C, Jiao J, Qin Y, Sang T, Ma Y, Wu M, Gao X, Cheng H, Yan Z, Li D, Sun H, Zhu F, Wang Y, Zeng L, Li Z, Zheng J, Xu K. Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Cancer Med. 2020 Aug;9(16):5827-5838. doi: 10.1002/cam4.3259. Epub 2020 Jul 1.
- 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. This study is not recruiting at the moment.
Shengqin Ye, M.D. principal investigator
Shanghai Longyao Biotechnology Inc., Ltd.
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 Mixed CD19/CD20 CAR-T Transfer in people with Recurrent or Refractory B Cell Malignancy, run by Shanghai Longyao Biotechnology Inc., 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 13 inclusion and 11 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 2 Jul 2017. 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?
Contact Xin Wang, M.D. (185-1602-2625 ext. +86, wangxin928@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall complete remission rate (time frame: Half a 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 NCT03207178, 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 2 Jul 2017.