Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
NCT ID: NCT02456350
Last Updated: 2016-08-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1
36 participants
INTERVENTIONAL
2015-04-30
2019-12-31
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Anti-CD19-CAR transduced T cells
Patients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells.
Fludarabine
On days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes.
Cyclophosphamide
On days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Anti-CD19-CAR transduced T cells
Modified cells will be infused IV over 30 minutes (2-4 days after the last dose of fludarabine).
Interventions
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Fludarabine
On days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes.
Cyclophosphamide
On days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Anti-CD19-CAR transduced T cells
Modified cells will be infused IV over 30 minutes (2-4 days after the last dose of fludarabine).
Eligibility Criteria
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Inclusion Criteria
2. Patients with CD19+ B cell malignancies are not able to receive standard treatments and willing to participate in the trial.
3. 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；
4. patients are not eligible for autologous or allogeneic stem-cell transplantation (SCT) or relapsed after autologous or allogeneic stem-cell transplantation；
5. 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.
6. Willing to sign a durable power of attorney；
7. Able to understand and sign the Informed Consent Document；
8. Performance status：ECOG 0-2；
9. Life expectancy：More than 3 months；
10. Patients of both genders must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen；
11. 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；
12. There is no obvious dysfunctions in heart , liver and kidney, and the functions of vital organs are normal；
13. Serology： (1) Seronegative for HIV antibody； (2) Seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV).
14. 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。
15. 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）。
16. 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)；
17. 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.
Exclusion Criteria
2. Patients that have active hemolytic anemia；
3. 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；
4. Women of child-bearing potential who are pregnant or breastfeeding；
5. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
7. Concurrent opportunistic infections；
8. Concurrent Systemic steroid therapy；
9. History of severe immediate hypersensitivity reaction to any of the agents used in this study；
10. Patients with central nervous system (CNS) metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions)；
11. 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；
12. Patients with cardiac atrial or cardiac ventricular lymphoma involvement；
13. Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment；
14. Previous treatment with any gene therapy products.
1 Year
85 Years
ALL
No
Sponsors
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Shenzhen Institute for Innovation and Translational Medicine
OTHER
Shenzhen Second People's Hospital
OTHER
Responsible Party
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Locations
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Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong, China
Countries
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Central Contacts
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Facility Contacts
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References
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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.
Other Identifiers
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201504001
Identifier Type: -
Identifier Source: org_study_id
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