To Evaluate the Safety and Efficacy of Human CD19 Targeted DASH CAR-T Cells Injection for Subjects With R/R B-ALL

NCT05651191 | Unknown Early Phase 1

• 1 other identifier: HRAIN01-ALL04-POC
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of human CD19 targeted DASH CAR-T Cells injection, and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory B-cell acute lymphoblastic leukemia.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

CD19; CAR-T; B-cell acute lymphoblastic leukemia; Relapsed /Refractory

Outcome Measures

Primary Outcomes (1)

• Dose limited toxicity (DLT)

  Safety Indicators

  28 days post infusion

Secondary Outcomes (7)

• Pharmacokinetics parameters - the highest concentration of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion

  2 years post infusion

• Pharmacokinetics parameters - the time to reach the highest concentration of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion

  2 years post infusion

• Pharmacokinetics parameters - the 28-day area under the curve of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion

  2 years post infusion

• Pharmacodynamics characteristics - the detection values of IL-6, IFN-γ, IL-15 cytokines in peripheral blood

  2 years post infusion

• Overall response rate (ORR, include CR and CRi) after administration

  3 months post infusion

Study Arms (1)

Human CD19 Targeted DASH CAR-T Cells Injection

EXPERIMENTAL

Single administration：0.5×10\^6 CAR+T, 1.0×10\^7 CAR+T, 2.0×10\^7 CAR+T

Drug: Human CD19 Targeted DASH CAR-T Cells Injection

Interventions

Human CD19 Targeted DASH CAR-T Cells Injection DRUG

Autologous genetically modified anti-CD19 CAR transduced T cells

Also known as: CD19 DASH CAR-T

Human CD19 Targeted DASH CAR-T Cells Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 70 years old (including cut-off value), Male and female;
• Expected survival \> 12 weeks;
• ECOG score 0-1;
• Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia, CD19 positive, and who met one of the following conditions:
• 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;
• 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);
• Those who relapse after stem cell transplantation are not affected by previous treatments;
• The venous access required for collection can be established and leukapheresis can be carried according to the judgement of investigators;
• Liver, kidney and cardiopulmonary functions meet the following requirements:
• Serum creatinine ≤ 1.5×ULN;
• Left ventricular ejection fraction \> 50%;
• Baseline oxygen saturation \> 96%;
• Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN (As judged by the investigator, the elevation of transaminase caused by the ALL disease itself, ALT and AST ≤ 5×ULN);
• Able to understand and sign the Informed Consent Document.

You may not qualify if:

• Graft-versus-host disease (GVHD), or need to use immunosuppressants after transplantation;
• Patients with hyperleukocytosis (white blood cell count ≥ 50×10\^9/L) or whose disease progressed rapidly according to the investigator's judgment at the time of enrollment and cannot ensure the completion of a complete treatment cycle;
• 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, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection;
• Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer detection higher than the lower limit of the research center can detect; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis detection positive;
• 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;
• Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
• 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;
• Received CAR-T treatment or other gene therapies before enrollment;
• Patients with symptoms of central nervous system;
• 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);
• The investigators consider other conditions unsuitable for enrollment.

Sponsors & Collaborators

• Hrain Biotechnology Co., Ltd.: lead
• Second Affiliated Hospital of Nanchang University: collaborator

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Qingming Wang, M.D.

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuedong Sun, M.D.

CONTACT

0086-021-58552006; sunxuedong@dashengbio.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 14, 2022
• Study Start: October 21, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2025
• Last Updated: December 14, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)