Immunotherapy With CD19 CAR T-cells for B-Cell Lymphoma, ALL and CLL

Phase 1

• Conditions: Leukemia; Lymphoma
• Interventions: Biological: Anti-CD19-CAR

• Registration Number: NCT02546739
• Lead Sponsor: Beijing Doing Biomedical Co., Ltd.

Brief Summary

This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in patients with high risk, relapsed CD19+ haematological malignancies.

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product named CD19 Chimeric Antigen Receptor (CAR) T-cells (CD19 CAR T-cells) in patients with high risk, relapsed CD19+ haematological malignancies (Leukemia and lymphoma). Following informed consent and registration to the trial, patients will undergo an unstimulated leukapheresis for the generation of the CD19 CAR T-cells. Patients will receive the CD19CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19 CAR T-cells in patients with high risk relapsed CD19+ malignancies.

Study Timeline

• Study First Submitted: 2015-09-08
• Study First Submitted QC: 2015-09-09
• Study First Posted: 2015-09-11
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-23
• Last Update Posted: 2021-01-26
• Study Start: 2021-03-01
• Primary Completion: 2022-03-01
• Study Completion: 2023-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphoblastic leukemia(CLL) and non-hodgkin lymphoma.
2. KPS>60.
3. Life expectancy>3 months.
4. Gender unlimited, age from 18 years to 70 years.
5. CD19 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 30% by flow cytometry.
6. Patients who have failed at least one line of a standard treatment.
7. No serious mental disorder.
8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L).
9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
10. No other tumors.
11. Patients volunteer to participate in the research.
12. Patients with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to trial.

Exclusion Criteria

1. KPS<50.
2. Patients are allergic to cytokines.
3. Central nervous system leukemia within 28 days.
4. Uncontrolled active infection.
5. Acute or chronic GVHD.
6. Treated with T cell inhibitor.
7. Pregnancy and nursing females.
8. HIV/HBV/HCV Infection.
9. Other situations we think improper for the research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: 2	Anti-CD19-CAR	Chronic lymphoblastic leukemia with chimeric antigen receptor modified T cells(Anti-CD19-CAR) targeting CD19.
Experimental: 1	Anti-CD19-CAR	Acute lymphoblastic leukemia treated with chimeric antigen receptor modified T cells(Anti-CD19-CAR) targeting CD19.
Experimental: 3	Anti-CD19-CAR	Non-hodgkin lymphoma treated with chimeric antigen receptor modified T cells(Anti-CD19-CAR) targeting CD19.

Primary Outcome Measures

Name	Time	Method
Adverse events of each patient.	3 years	Determine the toxicity profile of the CD19 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

Name	Time	Method
Antitumor Effects	Every 3 months post treatment up to 24 months	Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.
Survival time of Anti-CD19 CAR T cells in vivo.	3 years	To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.
Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	4 weeks	Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.

Trial Locations

Locations (12)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Hebei Yanda Ludaopei Hospital; 🇨🇳 Sanhe, Hebei, China

First Affiliated Hospital of Henan University of Science and Technology; 🇨🇳 Luoyang, Henan, China

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Huai'An First People'S Hospital; 🇨🇳 Huaian, Jiangsu, China

Nanjing Drum Tower Hospital; 🇨🇳 Nanjing, Jiangsu, China

First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Tianjin people's hospital; 🇨🇳 Tianjin, Tianjin, China

Shanxi Dayi Hospital; 🇨🇳 Taiyuan, Shanxi, China

Hangzhou Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Beijing DOING Biomedical Co., Ltd; 🇨🇳 Beijing, China