CD19 CAR-T Cell Therapy for Relapsed/Refractory B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia

A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor With Synthetic Biology Optimizing Nano-vector T Cells Injection for Subjects With Relapsed/Refractory/High-risk B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia

The primary objective of this study is to evaluate the safety and clinical activity of anti-CD19 Chimeric Antigen Receptor T cells (KD-019 CAR-T)infusion in the treatment of relapsed/refractory B-cell Lymphoma and B-cell acute lymphoblastic leukemia （B-ALL）.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: Anti-CD19 CAR-T Cells Injection

Detailed Description

The investigators designed an KD-019 Chimeric Antigen Receptor(CAR) with FMC63 single-chain antibody fragment (Scfv). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expressing this CAR release relatively low levels of cytokines. Subjects with relapsed/refractory CD19-positive B-cell Lymphoma and B-ALL can participate if all eligibility criteria are met. Subjects receive chemotherapy prior to the infusion of KD-019 CAR-T cells. After the infusion, subjects will accept follow-up for side effects and effect of KD-019 CAR-T cells by the sponsor. Study procedures may be performed while hospitalized.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Recruiting
      • Kunming Yan'an Hospital, Oncology Department
      • Contact: Lan Shi; Phone Number: 86-18988158897; Email: shi_lanlan@yahoo.com
      • Contact: Jiabao Song; Phone Number: 86-15663656065; Email: jiabaosong668@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients or their legal guardians voluntarily participate and sign the Informed Consent Document;
2. 18 Years and older, Male and female;
3. Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program;

B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types:

1. B-cell acute lymphoblastic leukemia;
2. Indolent B-cell lymphomas;
3. Aggressive B-cell lymphoma; 4、 Subjects:

(1) Residual lesions remain after treatment; (2) Not suitable for Hematopoietic stem cell transplantation (auto/allo-HSCT); (3) Relapse after Complement receptor 1 (CR1) and unsuitable for HSCT; (4) Patients with high risk factors; (5) Relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy.

5、 Have measurable or evaluable tumor foci; 6、 Liver, kidney and cardiopulmonary functions meet the following requirements:

1. Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN);
2. Total bilirubin ≤34.2μmol/L;
3. Serum creatinine<220μmol/L;
4. Baseline oxygen saturation≥95%;
5. Left ventricular ejection fraction（LVEF）≥40%. 7、 Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss); 8、Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 9、Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2，Expected survival≥3 months;

Exclusion Criteria:

1. Pregnant (urine/blood pregnancy test positive) or lactating women;
2. Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;
3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment;
4. Active or uncontrollable infection within four weeks prior to enrollment;
5. Patients with active hepatitis B/C;
6. HIV-infected patients;
7. Severe autoimmune or immunodeficiency disorders;
8. Patients are allergic to macromolecule drugs such as antigens or cytokines;
9. Subjects participated in other clinical trials within 6 weeks before enrollment;
10. Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
11. Mental illness;
12. Drug abuse/addiction;
13. The investigators consider other conditions unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anti-CD19 CAR-T Cells Injection; Dosage form：injection Dosage:1-5x10^6/kg, 70ml/time, The CAR-T cells will be administered by i.v. injection over 20-30 minutes Frequency: total one time	Biological: Anti-CD19 CAR-T Cells Injection; Autologous genetically modified anti-CD19 CAR transduced T cells; Other Names: KD-019 CAR-T cells Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.	The severe CRS post KD-019 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined.	0 to 14 days post infusion
Copies numbers of CAR in peripheral blood (PB)	Copies numbers of CAR in peripheral blood (PB)	1 year post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason	2 years post infusion
Duration of Response after administration	Duration of Response after administration	2 years post infusion
Progress Free Survival after administration	Progress Free Survival after administration	2 years post infusion

Collaborators and Investigators

• Sponsor: Yan'an Affiliated Hospital of Kunming Medical University
• Collaborators: KAEDI
• Investigators: Study Director: Peixian Zhang, Kunming Yan'an Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ANTICIPATED): August 1, 2021
• Study Completion (ANTICIPATED): August 1, 2022

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (ACTUAL): February 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: 201707202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No