Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
Genetically Engineered T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor for Treatment of Patients With B Cell Malignancies
1 other identifier
interventional
36
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2015
CompletedFirst Submitted
Initial submission to the registry
May 12, 2015
CompletedFirst Posted
Study publicly available on registry
May 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedAugust 3, 2016
August 1, 2016
4.7 years
May 12, 2015
August 1, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
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.
8 weeks
Secondary Outcomes (1)
Number of participants with Clinical responses
2 years
Study Arms (1)
Anti-CD19-CAR transduced T cells
EXPERIMENTALPatients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells.
Interventions
On days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes.
On days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Modified cells will be infused IV over 30 minutes (2-4 days after the last dose of fludarabine).
Eligibility Criteria
You may qualify if:
- 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；
- 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）。
- +3 more criteria
You may not qualify if:
- 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)；
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong, 518035, China
Related Publications (1)
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.
PMID: 35126471DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2015
First Posted
May 28, 2015
Study Start
April 1, 2015
Primary Completion
December 1, 2019
Study Completion
December 1, 2019
Last Updated
August 3, 2016
Record last verified: 2016-08