Cytoplasmic Activated PD-1 CAR T Cells in Refractory/Relapsed B Cell Lymphoma

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-12

Study Completion Date

2020-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

MC-19PD1 CAR-T in Relapsed or Refractory B Cell Lymphoma

NCT03932955

Lymphoma

UNKNOWN PHASE1

Clinical Study of Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Relapsed/Refractory Non-Hodgkin Lymphoma

NCT05420493

Relapsed Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Non Hodgkin Lymphoma

RECRUITING PHASE1

PD1-CD19-CART in Patients With r/r B-cell Lymphoma

NCT04213469

B-cell Lymphoma

COMPLETED NA

The Safety and Efficacy of CART-19 Cells in Relapse and Refractory Patients With CD19+ B-cell Lymphoma

NCT03101709

B Cell Lymphoma

UNKNOWN PHASE1

CD19 CART Cells for Patients With Relapse and Refractory CD19+ B-cell Lymphoma.

NCT03146533

B Cell Lymphoma

UNKNOWN PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Although CAR19 T cell therapy brings hope, the patients with refractory/relapsed B-cell lymphoma is still a problem for the current treatment. There are still some patients with poor therapeutic efficacy, and the efficacy of CAR19-T cell therapy remains to be improved. Basic research shows that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. However, the regimen of CAR19-T cells combined anti-PD1 inhibitors need to be combined with the application of anti-PD1 antibody and culture of CART cells during the treatment, there may be adverse events to PD1 antibodies. In this study, CAR19T cells carrying cytosolic activated PD1 possess the dual effects of CAR19T cells and anti-PD1 or anti-PD-L1 antibodies while overcoming the adverse events of anti-PD1 inhibitors, and might have better efficacy than conventional CAR19T cells plus anti-PD1 or anti-PD-L1 antibody treatment, with fewer side effects.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Relapsed Non Hodgkin Lymphoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Intervention Model

SEQUENTIAL

CAR19 T cell therapy improves the clinical efficacy of refractory/relapsed B-cell lymphoma, and the combined PDL1 inhibitors may further improve the efficacy of CD19 CART in the treatment of lymphomas. The clinical efficacy of KITE's CAR19 T cells and PD-L1 inhibition was reported. This phase 1 study was conducted in 9 patients with DLBCL, 8 patients got remission and during which 5 got complete remission. However, this type of treatment requires more data and observation in a larger sample of patients. In addition, Kite Pharmaceuticals' CD19 CART is priced at 370,000 US dollars. The cost of immune checkpoint inhibitors is also very expensive. Only very small proportion of patients could afford for that expenses. In this study, genetically engineered CAR T cells, which carry cytoplasmic activated PD1, are not inhibited by PDL1 molecules, will avoid the simultaneous application of immune checkpoint antibodies and the according adverse events.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CAR19 T cells carrying cytoplasmic activated PD-1

patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells.

Group Type EXPERIMENTAL

CAR19 T cells carrying cytoplasmic activated PD-1

Intervention Type DRUG

step 1: Collect 50-100ml of peripheral blood for culture of CAR19 T cells carrying cytoplasmic activated PD-1 step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 2x106 /kg for the first 3 patients, 6x106 /kg for the second 3 patients and 18x106 /kg for the third 3 patients.

After finishing this, another 6 patients will be enrolled for observation of efficacy.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CAR19 T cells carrying cytoplasmic activated PD-1

step 1: Collect 50-100ml of peripheral blood for culture of CAR19 T cells carrying cytoplasmic activated PD-1 step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 2x106 /kg for the first 3 patients, 6x106 /kg for the second 3 patients and 18x106 /kg for the third 3 patients.

After finishing this, another 6 patients will be enrolled for observation of efficacy.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 18-70 years old and the expected lifetime \>3 months
* Refractory/relapsed CD19 positive B cell lymphoma by pathology
* ECOG score \<2
* Measureable lesions according to RECIST 1.1
* Sufficient heart, liver, kidney and bone marrow function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN; bone marrow: WBC ≥ 2.0 × 109/L, Hb ≥ 80 g/L, PLT ≥ 30 × 109/L)
* no serious allergies
* No other serious diseases that conflict with this protocol (eg, autoimmune diseases, immunodeficiency, organ transplantation)
* No other history of malignancy
* No serious mental disorders
* Women of childbearing age must be negative for blood pregnancy test within 7 days and must take appropriated contraceptive measures during and 3 months after the study
* The patient himself agrees to participate in this clinical study and signed the "informed consent"

Exclusion Criteria

* Lactating women
* Severe infectious or viral diseases (HIV positive, syphilis, etc.)
* Active hepatitis B or C viral hepatitis
* Patients who used high-dose glucocorticoids within 1 week
* Participation in other clinical studies in the past 3 months or having been treated with other gene products

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No