Leukemia, Lymphocytic, Chronic, B-CellPhase 1/2NCT02782351
Humanized CAR-T Therapy for Treatment of B Cell Malignancy
A Phase 1/2 study testing CAR-T in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Kai Lin Xu; Jun Nian Zheng at 2 sites in China.
Trial summary
The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- CAR-T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesChina
- Study dates
- May 2016to Dec 2018
- 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age≥3 at the time of consent
- Survival time>12 weeks
- B cell hematological malignancies by pathological examination
- Chemotherapy failure or recurrent B cell malignancy
- Creatinine< 2.5mg/dl
- Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level
Show all 11Show fewer
- Karnofsky Performance Status>50% at the time of screening
- Bilirubin<2.0mg/dl
- Adequate pulmonary, renal, hepatic, and cardiac function
- Fail in autologous or allogenic haemopoietic stem cell transplantation
- Free of leukocytes removal contraindications
Who cannot join
- Pregnant or nursing women
- Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- Previous treatment with any gene therapy product
- Abnormal vital signs
- Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2
- General infection or local severe infection, or other infection that is not controlled
Show all 9Show fewer
- Dysfunction in lung, heart, kidney and brain.
- Severe autoimmune diseases
- other symptoms that are not applicable for CAR-T
Trial locations and contacts
2 sites in 1 country.
JunNian Zheng, M.D., Ph.D. contact
China2 sites, 2 recruiting
- Recruiting
Huaian First People's Hospital
Huai'an, Jiangsu, 223300
Chunling Wang, M.D., Ph.D.
- Recruiting
Affiliated hospital of Xuzhou medical college
Xuzhou, Jiangsu, 221000
Jiang Cao, M.D., Ph.D.
About this study
Official title: Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19
The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells.
Read the detailed description
CD19 has been extensively evaluated as a therapeutic target for recurrent or refractory B cell malignancy by chimeric antigen receptor T cell therapy, the single chain antibody sequence (scFv) against CD19 derived from a mouse hybridoma was widely employed. However, the immunogenicity of the mouse scFv sequence might be one of the reasons that CAR-T cells cannot persist in vivo for long. In present study investigators replace the mouse-derived scFv with a a humanized one and evaluate its safety and efficacy.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- CAR-T
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-TBiological
Patients will be infused with autologous CAR-T infusion in a dose escalating manner.
| Study group | Role | What they receive |
|---|---|---|
| CAR-T | Experimental | In interventional studies, patients enrolled will receive autologous 2nd generation CAR-T cells, which contain a humanized single chain antibody sequence against CD19. Receives: Biological: CAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAR-T cells persistence in peripheral blood
The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR
Measured: 12 months
Secondary outcomes (1)
B cell number and immunoglobulins in peripheral blood
The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2016 (estimated)
- Study startMay 2016
- Primary completionJun 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kai Lin Xu; Jun Nian Zheng
- Sponsor type
- University, hospital or other
- Collaborators
- iCarTAB BioMed Inc., Huai'an First People's Hospital
- Responsible party
- Sponsor-investigator, Kai Lin Xu; Jun Nian Zheng, Xuzhou Medical University
- Investigators
- KaiLin Xu, MD. Ph.D., Principal investigator, Xuzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02782351
- Sponsor's protocol ID
- XYFY2016-KL002-01
- Status last verified
- Aug 2017
- First submitted
- 17 May 2016
- Last updated
- 4 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov. 2015 Jul;14(7):499-509. doi: 10.1038/nrd4597.
PubMed 26129802Davila ML, Bouhassira DC, Park JH, Curran KJ, Smith EL, Pegram HJ, Brentjens R. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies. Int J Hematol. 2014 Apr;99(4):361-71. doi: 10.1007/s12185-013-1479-5. Epub 2013 Dec 6.
PubMed 24311149Qi Y, Zhao M, Hu Y, Wang Y, Li P, Cao J, Shi M, Tan J, Zhang M, Xiao X, Xia J, Ma S, Qiao J, Yan Z, Li H, Pan B, Sang W, Li D, Li Z, Zhou J, Huang H, Liang A, Zheng J, Xu K. Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood. 2022 Jun 9;139(23):3376-3386. doi: 10.1182/blood.2021013733.
PubMed 35338773Chen W, Ma Y, Shen Z, Chen H, Ma R, Yan D, Shi M, Wang X, Song X, Sun C, Cao J, Cheng H, Zhu F, Sun H, Li D, Li Z, Zheng J, Xu K, Sang W. Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy. Front Immunol. 2021 Oct 29;12:755549. doi: 10.3389/fimmu.2021.755549. eCollection 2021.
PubMed 34777367
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19
- ClinicalTrials.gov ID
- NCT02782351
- Acronym / sponsor ID
- XYFY2016-KL002-01
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Kai Lin Xu; Jun Nian ZhengUniversity, hospital or other
- Collaborators
- iCarTAB BioMed Inc., Huai'an First People's Hospital
- Study start
- May 2016
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 25 May 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 present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells.
Detailed description
CD19 has been extensively evaluated as a therapeutic target for recurrent or refractory B cell malignancy by chimeric antigen receptor T cell therapy, the single chain antibody sequence (scFv) against CD19 derived from a mouse hybridoma was widely employed. However, the immunogenicity of the mouse scFv sequence might be one of the reasons that CAR-T cells cannot persist in vivo for long. In present study investigators replace the mouse-derived scFv with a a humanized one and evaluate its safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T | Experimental | Biological: CAR-TIn interventional studies, patients enrolled will receive autologous 2nd generation CAR-T cells, which contain a humanized single chain antibody sequence against CD19. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Age≥3 at the time of consent
- Survival time>12 weeks
- B cell hematological malignancies by pathological examination
- Chemotherapy failure or recurrent B cell malignancy
- Creatinine< 2.5mg/dl
Key exclusion criteria (9 listed)
- Pregnant or nursing women
- Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- Previous treatment with any gene therapy product
- Abnormal vital signs
- Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2
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 |
|---|---|---|
| CAR-TPatients will be infused with autologous CAR-T infusion in a dose escalating manner. | Biological | CAR-T |
Primary outcome
CAR-T cells persistence in peripheral blood
Time frame: 12 months
The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR
1 secondary outcome
B cell number and immunoglobulins in peripheral blood
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2017.
- Background: PubMed 26129802van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov. 2015 Jul;14(7):499-509. doi: 10.1038/nrd4597.
- Results publication: PubMed 24311149Davila ML, Bouhassira DC, Park JH, Curran KJ, Smith EL, Pegram HJ, Brentjens R. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies. Int J Hematol. 2014 Apr;99(4):361-71. doi: 10.1007/s12185-013-1479-5. Epub 2013 Dec 6.
- Derived from this study: PubMed 35338773Qi Y, Zhao M, Hu Y, Wang Y, Li P, Cao J, Shi M, Tan J, Zhang M, Xiao X, Xia J, Ma S, Qiao J, Yan Z, Li H, Pan B, Sang W, Li D, Li Z, Zhou J, Huang H, Liang A, Zheng J, Xu K. Efficacy and safety of CD19-specific CAR T cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood. 2022 Jun 9;139(23):3376-3386. doi: 10.1182/blood.2021013733.
- Derived from this study: PubMed 34777367Chen W, Ma Y, Shen Z, Chen H, Ma R, Yan D, Shi M, Wang X, Song X, Sun C, Cao J, Cheng H, Zhu F, Sun H, Li D, Li Z, Zheng J, Xu K, Sang W. Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy. Front Immunol. 2021 Oct 29;12:755549. doi: 10.3389/fimmu.2021.755549. eCollection 2021.
- Individual participant dataSharing planned: Yes
Related trials for Leukemia, Lymphocytic, Chronic, B-Cell
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
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.
JunNian Zheng, M.D., Ph.D. contact
KaiLin Xu, MD. Ph.D. principal investigator
Xuzhou Medical University
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 CAR-T in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Kai Lin Xu; Jun Nian Zheng 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 11 inclusion and 9 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 4 Aug 2017. 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?
Contact Jiang Cao, M.D., Ph.D. (8651685802291, zimu05067@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CAR-T cells persistence in peripheral blood (time frame: 12 months). 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 NCT02782351, which also lists 4 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 4 Aug 2017.