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

A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Human CD19 Targeted T Cells Injection for Subjects With Relapsed and Refractory CD19-positive B-cell Acute Lymphoblastic Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; CD19-positive
• Intervention / Treatment: Drug: Human CD19 targeted T Cells Injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hongliang Fang, doctor; Phone Number: 021-58552006; Email: fanghongliang@dashengbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
      • Contact: Xianmin Song, Professor; Phone Number: 3173 021-63240090; Email: shongxm@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human CD19 targeted T Cells Injection	Drug: Human CD19 targeted T Cells Injection; Autologous genetically modified anti-CD19 CAR transduced T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DLT	28 days post infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of CAR-positive T cells in circulation	2 years post infusion
The concentration of CD19-positive B cells in peripheral blood.	2 years post infusion
Overall response rate (ORR) after administration	90 days post infusion
Duration of remission (DOR) after administration	2 years post infusion
Progress Free Survival (PFS) after administration	2 years post infusion
Overall Survival (OS)after administration	2 years post infusion
The immunogenicity of Human CD19 targeted T Cells Injection. (the detection of human anti-mouse antibody)	2 years post infusion

Collaborators and Investigators

• Sponsor: Hrain Biotechnology Co., Ltd.
• Collaborators: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 29, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: CAR-T; CD19; leukemia; B-ALL; Relapsed /Refractory
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: HRAIN01-ALL01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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