Chronic Lymphocytic LeukemiaPhase 1NCT02456350
Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
A Phase 1 study testing Fludarabine, Cyclophosphamide and Anti-CD19-CAR transduced T cells in people with Chronic Lymphocytic Leukemia and Acute Lymphocytic Leukemia, run by Shenzhen Second People's Hospital at 1 site in China.
Trial summary
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) with a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. Read more about this study
- Who is it for?
- Ages 1 year to 85 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Acute Lymphocytic Leukemia, Lymphoma
- What is being tested?
- Fludarabine, Cyclophosphamide and Anti-CD19-CAR transduced T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- Apr 2015to Dec 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 1 year to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and B cell lymphoma；
- Patients with CD19+ B cell malignancies are not able to receive standard treatments and willing to participate in the trial.
- Patients must have a 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 not eligible for autologous or allogeneic stem-cell transplantation (SCT) or relapsed after autologous or allogeneic stem-cell transplantation；
- Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease and no longer taking immunosuppressive agents during the treatment.
- Willing to sign a durable power of attorney；
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- Able to understand and sign the Informed Consent Document；
- Performance status：ECOG 0-2；
- Life expectancy：More than 3 months；
- Patients of both genders must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen；
- Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion, because of the potentially dangerous effects on the fetus；
- There is no obvious dysfunctions in heart , liver and kidney, and the functions of vital organs are normal；
- Serology： (1) Seronegative for HIV antibody； (2) Seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV).
- Hematology： (1) Absolute neutrophil count ≥ 1000/mm3 without support of filgrastim； (2) Platelet count ≥ 50,000/mm3； (3) Hemoglobin > 8.0g/dL； (4) lymphocyte count ≤ 4000/mm3。
- Chemistry： (1) AST and ALT ≤ 5 times upper limit of normal； (2) Serum creatinine ≤ 1.6 mg/dl； (3) Bilirubin ≤ 1.5 mg/dl（3.0 mg/dL in patients with Gilbert's syndrome）。
- More than three weeks must have elapsed since any prior systemic therapy at the time of randomization, and patients' toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo)；
- Normal cardiac ejection fraction and no evidence of pericardial effusion as determined by an echocardiogram；
- 18、More than 30 days must have elapsed since Monoclonal antibody therapy administered prior to apheresis.
Who cannot join
- Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
- Patients that have active hemolytic anemia；
- Patients with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases, or any residual intracranial implants；
- Women of child-bearing potential who are pregnant or breastfeeding；
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
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- Concurrent opportunistic infections；
- Concurrent Systemic steroid therapy；
- History of severe immediate hypersensitivity reaction to any of the agents used in this study；
- Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions)；
- CNS-3 disease or traumatic spinal tap with POSITIVE Steinherz/Bleyer algorithm with cerebral spinal fluid involvement with malignancy will make any patient not eligible for this protocol；
- Patients with cardiac atrial or cardiac ventricular lymphoma involvement；
- Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment；
- Previous treatment with any gene therapy products.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong, 518035
Mingjun Wang, M.D., Ph.D., 15814723218, mingjunw429@163.com
Weihong Chen, M.D., Ph.D., 13923871697, whitney-cindy@hotmail.com
About this study
Official title: Genetically Engineered T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor for Treatment of Patients With B Cell Malignancies
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) with a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.
Objectives:
Read more
To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.
Eligibility:
Patients between 1 and 85 years of age, who have relapsed or refractory CD19-expressing B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.
Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.
Patients must have adequate organ functions.
Design:
- Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding anti-CD19 CAR containing a CD28 and a CD3 zeta as costimulatory domains as well as a safety switch.
- Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
- Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
- Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Read the detailed description
Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 and CD3-zeta, and a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.
OBJECTIVES:
- Primary objectives
- To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
- Secondary objectives:
- To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
- To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells.
- Being tested
- Fludarabine, Cyclophosphamide, Anti-CD19-CAR transduced T cells
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
On days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes.
CyclophosphamideDrug
On days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Anti-CD19-CAR transduced T cellsBiological
Modified cells will be infused IV over 30 minutes (2-4 days after the last dose of fludarabine).
| Study group | Role | What they receive |
|---|---|---|
| Anti-CD19-CAR transduced T cells | Experimental | Patients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Anti-CD19-CAR transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
Measured: 8 weeks
Secondary outcomes (1)
Number of participants with Clinical responses
To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
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 posted28 May 2015 (estimated)
- Study startApr 2015
- 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 Chronic Lymphocytic LeukemiaStudies 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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen Second People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shenzhen Institute for Innovation and Translational Medicine
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456350
- Sponsor's protocol ID
- 201504001
- Status last verified
- Aug 2016
- First submitted
- 12 May 2015
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Zhou W, Chen W, Wan X, Luo C, Du X, Li X, Chen Q, Gao R, Zhang X, Xie M, Wang M. Benefits of Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma. Front Genet. 2022 Jan 20;12:815679. doi: 10.3389/fgene.2021.815679. eCollection 2021.
PubMed 35126471
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetically Engineered T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor for Treatment of Patients With B Cell Malignancies
- ClinicalTrials.gov ID
- NCT02456350
- Acronym / sponsor ID
- 201504001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Shenzhen Second People's HospitalUniversity, hospital or other
- Collaborators
- Shenzhen Institute for Innovation and Translational Medicine
- Study start
- Apr 2015
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 28 May 2015 (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.
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) with a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.
Objectives:
To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.
Eligibility:
Patients between 1 and 85 years of age, who have relapsed or refractory CD19-expressing B-cell malignancies (leukemia or lymphoma) that have not responded to standard treatments.
Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.
Patients must have adequate organ functions.
Design:
- Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding anti-CD19 CAR containing a CD28 and a CD3 zeta as costimulatory domains as well as a safety switch.
- Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
- Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
- Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Detailed description
Despite progress has been made to date in the treatment of patients with B cell malignancies, including leukemia and lymphoma, many patients with relapsed or refractory diseases do not respond to the standard treatments. It has been shown that anti-CD19 CAR-transduced T cells may be an effective approach to treat the relapsed or refractory diseases. The procedure involves collecting PBMCs from the patients and modifying the T cells to attack the malignant B cells. In this trial, autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) containing the signaling domains of CD28 and CD3-zeta, and a safety switch will be infused back to patients with B cell malignancies, including lymphoma and leukemia. The patients will be pretreated with a lymphodepleting preconditioning regimen before the infusion of anti-CD19 CAR T cells, and will be monitored for adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.
OBJECTIVES:
- Primary objectives
- To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
- Secondary objectives:
- To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
- To determine the in vivo persistency of the anti-CD19 CAR-transduced T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CD19-CAR transduced T cells | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Biological: Anti-CD19-CAR transduced T cellsPatients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells. |
Who may qualify
- Ages
- 1 year to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and B cell lymphoma；
- Patients with CD19+ B cell malignancies are not able to receive standard treatments and willing to participate in the trial.
- Patients must have a 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 not eligible for autologous or allogeneic stem-cell transplantation (SCT) or relapsed after autologous or allogeneic stem-cell transplantation；
- Patients with history of allogeneic stem cell transplantation are eligible, providing 6 months had elapsed from SCT, they have no evidence of active graft-versus-host disease and no longer taking immunosuppressive agents during the treatment.
Key exclusion criteria (14 listed)
- Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
- Patients that have active hemolytic anemia；
- Patients with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases, or any residual intracranial implants；
- Women of child-bearing potential who are pregnant or breastfeeding；
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
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 |
|---|---|---|
| FludarabineOn days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes. | Drug | Anti-CD19-CAR transduced T cells |
| CyclophosphamideOn days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine. | Drug | Anti-CD19-CAR transduced T cells |
| Anti-CD19-CAR transduced T cellsModified cells will be infused IV over 30 minutes (2-4 days after the last dose of fludarabine). | Biological | Anti-CD19-CAR transduced T cells |
Primary outcome
Number of participants with Adverse Events
Time frame: 8 weeks
To evaluate the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
1 secondary outcome
Number of participants with Clinical responses
Time frame: 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 Aug 2016.
- Derived from this study: PubMed 35126471Zhou W, Chen W, Wan X, Luo C, Du X, Li X, Chen Q, Gao R, Zhang X, Xie M, Wang M. Benefits of Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma. Front Genet. 2022 Jan 20;12:815679. doi: 10.3389/fgene.2021.815679. eCollection 2021.
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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.
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 Fludarabine, Cyclophosphamide and Anti-CD19-CAR transduced T cells in people with Chronic Lymphocytic Leukemia and Acute Lymphocytic Leukemia, run by Shenzhen Second People's Hospital 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 18 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: status not confirmed, as of the sponsor's last update on 3 Aug 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mingjun Wang, M.D., Ph.D. (15814723218, mingjunw429@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (time frame: 8 weeks). 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 NCT02456350, 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 3 Aug 2016.