To Evaluate the Safety and Tolerability of Human CD19-CD22 Targeted T Cells Injection for Subjects With R/R B-ALL.

NCT05223686 | Unknown Phase 1

• 1 other identifier: HRAIN01-ALL02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of Human CD19-CD22 Targeted T Cells Injection for the treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19-CD22 CAR+ T cells.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia; CD19-CD22; CAR-T; relapsed/refractory

Outcome Measures

Primary Outcomes (1)

• Dose limited toxicity(DLT)

  Safety indicators

  28 days post infusion

Secondary Outcomes (11)

• Adverse events；

  28 days post infusion

• Pharmacokinetic parameters: the highest concentration of anti-human CD19-CD22 T cells amplified in peripheral blood after reinfusion;

  2 years post infusion（the last subject will be followed up to 15 years after infusion）

• Pharmacokinetic parameters: the time to reach the highest concentration of anti-human CD19-CD22 T cells amplified in peripheral blood after reinfusion;

  2 years post infusion（the last subject will be followed up to 15 years after infusion）

• Pharmacokinetic parameters: the 28-day area under the curve of anti-human CD19-CD22 T cells amplified in peripheral blood after reinfusion;

  2 years post infusion（the last subject will be followed up to 15 years after infusion）

• Pharmacodynamic parameters: the detection counts of CD19 or CD22 positive B cells in peripheral blood;

  2 years post infusion（the last subject will be followed up to 15 years after infusion）

Study Arms (1)

Human CD19-CD22 Targeted T Cells Injection

EXPERIMENTAL

Single administration：1.0×10\^6 CAR+T, 3.0×10\^6 CAR+T，6.0×10\^6 CAR+T

Drug: Human CD19-CD22 Targeted T Cells Injection

Interventions

Human CD19-CD22 Targeted T Cells Injection DRUG

One time single predetermined dose level CAR-positive T cells will be utilized based on the NMPA approved product label.

Also known as: CD19-CD22 CAR-T

Human CD19-CD22 Targeted 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:

• Subjects with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia:
• \~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 or/and CD22 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 mononuclear cell collection can be determined by the investigators;
• Liver, kidney and cardiopulmonary functions meet the following requirements:
• Serum creatinine≤1.5×ULN;
• Left ventricular ejection fraction\>50%;
• Baseline blood oxygen saturation\>96%;
• Total bilirubin≤2×ULN; ALT and 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:

• Any one of the following conditions cannot be selected as a subject：
• 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 HBsAg or HBcAb and peripheral blood HBV DNA titer detection higher than the lower limit of the research center can detect; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis 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
• Ruijin Hospital: collaborator

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jianqing Mi, Doctor

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuedong Sun, Doctor

CONTACT

+8615811287219; sunxuedong@dashengbio.com

Study Design

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

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 4, 2022
• Study Start: February 10, 2022
• Primary Completion: June 10, 2023
• Study Completion: March 10, 2025
• Last Updated: February 4, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)