Human CD19 Targeted T Cells Injection Therapy for Relapsed and Refractory CD19-positive Leukemia

NCT ID: NCT03798509

Last Updated: 2021-08-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-13
• Study Completion Date: 2024-01-31

Brief Summary

To evaluate the safety and tolerance of human CD19 targeted T Cells injection for the treatment of relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.

Detailed Description

Participants with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, electrocardiograph and blood draws. Participants receive chemotherapy prior to the infusion of CD19 CAR+ T cells. After the infusion, participants will be followed for side effects and effect of CD19 CAR+ T cells. Study procedures may be performed while hospitalized.

Conditions

CD19-positive; Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Human CD19 targeted T Cells Injection

Group Type: EXPERIMENTAL

Human CD19 targeted T Cells Injection

Intervention Type: DRUG

Autologous genetically modified anti-CD19 CAR transduced T cells

Interventions

Human CD19 targeted T Cells Injection

Autologous genetically modified anti-CD19 CAR transduced T cells

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 18 to 70 Years Old, Male and female;

2. Expected survival > 12 weeks;

3. ECOG score 0-1;

4. Bone marrow examination clearly diagnosed as CD19 positive B-cell acute lymphoblastic leukemia and who met one of the following conditions:

1. Those who failed to achieve CR after at least 2 courses of standard chemotherapy or had early relapse after complete remission (<12 months) or late relapse after complete remission (≥ 12 months) and failed to achieve CR after 1 course of standard chemotherapy;

2. For Ph+ ALL: in addition to receiving at least 2 courses of standard chemotherapy, at least two TKIs should be treated with no complete remission or relapse after complete remission (Patients who cannot tolerate TKI therapy or have TKI treatment contraindications or have T315i mutation are excluded);

3. Those who relapse after stem cell transplantation are not affected by previous treatments;

5. The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;

6. Liver, kidney and cardiopulmonary functions meet the following requirements:

1. Creatinine is in the normal range;

2. Left ventricular ejection fraction >50%;

3. Baseline oxygen saturation>92%;

4. Total bilirubin ≤ 2×ULN; ALT and AST ≤2.5 × ULN;

7. Able to understand and sign the Informed Consent Document.

Exclusion Criteria

1. Graft-versus-host disease (GVHD), or need to use immunosuppressants;

2. Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;

3. Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;

4. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;

5. Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;

6. Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;

7. Received CAR-T treatment or other gene therapies before enrollment;

8. Patients with symptoms of central nervous system;

9. Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;

10. The investigators consider other conditions unsuitable for enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Hrain Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongliang Fang, doctor

Role: CONTACT

fanghongliang@dashengbio.com

021-58552006

Facility Contacts

Xianmin Song, Professor

Role: primary

shongxm@139.com

021-63240090 ext. 3173

References

Wang H, Tsao ST, Gu M, Fu C, He F, Li X, Zhang M, Li N, Hu HM. A simple and effective method to purify and activate T cells for successful generation of chimeric antigen receptor T (CAR-T) cells from patients with high monocyte count. J Transl Med. 2022 Dec 19;20(1):608. doi: 10.1186/s12967-022-03833-6.

Reference Type: DERIVED

PMID: 36536403 (View on PubMed)

Other Identifiers

HRAIN01-ALL01

Identifier Type: -

Identifier Source: org_study_id