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

Lymphoma Clinical Trial

Official title:

Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02546739
• Other study ID #: Doing-002
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: March 1, 2021
• Est. completion date: March 1, 2023

Study information

• Verified date: January 2021
• Source: Beijing Doing Biomedical Co., Ltd.
• Contact: gai liyun, doctor
• Phone: 086-13269099630
• Email: liyun_gai[@]doingtimes.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 1, 2023
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Lymphoma

Intervention

Biological:
• Anti-CD19-CAR
Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Beijing DOING Biomedical Co., Ltd	Beijing
China	First Hospital of Jilin University	Changchun	Jilin
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hangzhou Cancer Hospital	Hangzhou	Zhejiang
China	Huai'An First People'S Hospital	Huaian	Jiangsu
China	First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Hebei Yanda Ludaopei Hospital	Sanhe	Hebei
China	Shanxi Dayi Hospital	Taiyuan	Shanxi
China	Tianjin people's hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (3)

Lead Sponsor	Collaborator
Beijing Doing Biomedical Co., Ltd.	First Hospital of Jilin University, Hebei Yanda Ludaopei Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events of each patient.	Determine the toxicity profile of the CD19 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	3 years
Secondary	Survival time of Anti-CD19 CAR T cells in vivo.	To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.	3 years
Secondary	Antitumor Effects	Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.	Every 3 months post treatment up to 24 months
Secondary	Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	4 weeks