Clinical trial NCT03191773: A Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies
Official title: A Prospective, Multicenter, Single-Arm Study of Anti-CD19 CAR-T Cell Immunotherapy for Refractory /Relapsed B Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Lymphocytic Leukemia
Chronic Lymphocytic Leukemia
Lymphoma
Lead sponsor: Second Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Shenzhen Institute for Innovation and Translational Medicine
name: Guangzhou First People's Hospital
name: First People's Hospital of Foshan
name: Dongguan People's Hospital
name: The First Affiliated Hospital of Guangdong Pharmaceutical University
First posted: 2017-06-19
Enrollment: 100
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Autologous T cells engineered to express an anti-CD19 chimeric antigen receptor (CAR) will be infused back to patients with refractory /relapsed B cell malignancies, including lymphoma and leukemia. The patients will be monitored after infusion of anti-CD19 CAR-transduced T cells for safety,adverse events, persistence of anti-CD19 CAR-transduced T cells and treatment efficacy.

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 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 safety, adverse events, persistence of anti-CD19 CAR-transduced T cells and the treatment efficacy.

Eligibility criteria: Inclusion Criteria:

1. Patients must have a CD19+ B cell malignancy，including relapsed or refractory B cell leukemia and/or B cell lymphoma；
2. 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；
3. 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 (GVHD) and no longer taking immunosuppressive agents during the treatment;
4. Able to understand and sign the Informed Consent Document；
5. There is no obvious dysfunctions in heart , liver, lung, kidney, and performance status with ECOG \< 2；
6. Life expectancy：More than 3 months for leukemia and more than 6 months for lymphoma.

Exclusion Criteria:

1. Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression；
2. Patients that have active hemolytic anemia；
3. Patients who have uncontrollable infectious diseases within 2 weeks before enrollment;
4. Patients with human immunodeficiency virus (HIV) antibody seropositive;
5. Active infection of Hepatitis B virus and / or hepatitis C virus;
6. Patients with any residual intracranial implants；
7. Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
8. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
9. Concurrent opportunistic infections；
10. Concurrent systemic steroid therapy；
11. History of severe immediate hypersensitivity reaction to any of the agents used in this study；
12. Women of child-bearing potential who are pregnant or breastfeeding；
13. Patients with cardiac atrial or cardiac ventricular lymphoma involvement；
14. Other anti-neoplastic investigational agents currently or within 30 days prior to start of the treatment；
15. Psychiatric patients;
16. Previous treatment with any gene therapy products.

Primary outcomes:
measure: Number of participants with Adverse Events
timeFrame: 24 months
measure: Number of participants with clinical responses
timeFrame: 24 months
Secondary outcomes:
measure: Evaluation of overall survial
timeFrame: 24 months
Other outcomes:
Locations:
city: Dongguan
country: China
facility: Department of Hematology, Dongguan People's Hospital
state: Guangdong
city: Foshan
country: China
facility: Department of Hematology, the First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Department of Hematology, Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Department of Hematology, The First Affiliated Hospital of Guangdong Pharmaceutical University
state: Guangdong
city: Guangzhou
country: China
facility: Department of Hematology,the Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Second Affiliated Hospital of Guangzhou Medical University
name: Ying Feng, MD
role: STUDY_DIRECTOR
affiliation: Shenzhen Institute for Innovation and Translational Medicine
name: Mingjun Wang, MD
role: STUDY_DIRECTOR
References: