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

NCT03540303 | Unknown Phase 1 DMC

• 1 other identifier: HenanCH CAR 2-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Relapsed Non Hodgkin Lymphoma

Keywords

relapsed/refractory, B cell, lymphoma, CAR

Outcome Measures

Primary Outcomes (1)

• safety: occurrence of study related adverse events

  occurrence of study related adverse events

  6 months

Secondary Outcomes (1)

• objective response rate

  3 months and 6 months

Study Arms (1)

CAR19 T cells carrying cytoplasmic activated PD-1

EXPERIMENTAL

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

Drug: CAR19 T cells carrying cytoplasmic activated PD-1

Interventions

CAR19 T cells carrying cytoplasmic activated PD-1 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.

CAR19 T cells carrying cytoplasmic activated PD-1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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"

You may not qualify if:

• 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

Sponsors & Collaborators

• Henan Cancer Hospital: lead
• The Pregene (ShenZhen) Biotechnology Company, Ltd.: collaborator

Study Sites (1)

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yongping Song, M.D

  Henan Cancer Hospital

  STUDY CHAIR

Central Study Contacts

Yongping Song, M.D

CONTACT

+86-371-65587199; songyongping2018@126.com

Quanli Gao, M.D

CONTACT

+86-15038171966; gaoquanli2015@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: May 30, 2018
• Study Start: April 12, 2018
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: May 30, 2018

Record last verified: 2018-04

Locations

CN (1)