Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies
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|ClinicalTrials.gov Identifier: NCT03076437|
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : March 10, 2017
Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) 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.
To evaluate the safety and the efficacy of anti-CD19 CAR-transduced T cell therapy for patients with B cell malignancies.
Patients between 1 and 80 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.
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 or 4-1BB and a CD3 zeta as costimulatory domains.
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Lymphoma||Combination Product: Drugs and Anti-CD19-CAR transduced T cells||Phase 1 Phase 2|
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 or 4-1BB and CD3-zeta 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.
To determine the safety and feasibility of the administration of anti-CD19 CAR transduced T cells in patients with CD19+ B-cell malignancies.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Anti-CD19 Chimeric Antigen Receptor (CAR)-Transduced T Cell Therapy for Patients With B Cell Malignancies|
|Actual Study Start Date :||January 15, 2016|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
Experimental: Anti-CD19-CAR transduced T cells
Patients will receive a lymphodepleting preconditioning regimen followed by anti-CD19- CAR-transduced T cells.
Drug: Fludarabine Drug: Cyclophosphamide Biological: Anti-CD19-CAR transduced T cells
Combination Product: Drugs and Anti-CD19-CAR transduced T cells
Drug: Fludarabine On days -4 through -2, Fludarabine 30mg/m2 IV will be infused over 30 minutes. Drug: Cyclophosphamide On days -4 through -2, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.
Biological: Anti-CD19-CAR transduced T cells Modified cells will be infused IV over 30 minutes (1-3 days after the last dose of fludarabine).
- 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.
- Number of participants with Clinical responses [ Time Frame: 2 years ]To determine if the treatment regimen can result in clinical regression of B-cell malignancies in the patients as described above.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076437
|Contact: Mingjun Wang, MD,PhDemail@example.com|
|Contact: Yirong Jiang, MDfirstname.lastname@example.org|
|Department of Hematology, Dongguan People's Hospital||Recruiting|
|Dongguan, Guangdong, China, 523059|
|Contact: Yirong Jiang, MD 13688967985 email@example.com|
|Contact: Mingjun Wang, MD, PhD 15814723218 firstname.lastname@example.org|
|Principal Investigator: Yirong Jiang, MD|
|Principal Investigator:||Mingjun Wang, MD,PhD||Shenzhen Institute for Innovation and Translational Medicine|
|Principal Investigator:||Yirong Jiang, MD||Dongguan People's Hospital|