Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Acute B Lymphocytic Leukemia

NCT04714593 | Unknown Phase 1

• 1 other identifier: CAR-T SXZL02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation the safety,tolerability, preliminary efficacy,and PK/PD of CD19-CD22 CAR-T cells for the treatment of acute B lymphocytic leukemia.

Conditions

Acute Lymphocytic Leukemia， B-Cell

Outcome Measures

Primary Outcomes (2)

• DLT

  Observe wether dose limiting toxicity will happened in dose escalation phase

  Form infusion CAR-T cells to 28 days after infusion

• ORR

  The overall response rate after CD19-CD22 CAR-T Cells immunotherapy

  Form infusion CAR-T cells to 2 years after infusion

Secondary Outcomes (12)

• Incidence of various types of adverse recation

  Form infusion CAR-T cells to 2 years after infusion

• PFS

  Form infusion CAR-T cells to 2 years after infusion

• DOR

  Form infusion CAR-T cells to 2 years after infusion

• OS

  Form infusion CAR-T cells to subjects died，assessed up to 60 months

• Cmax

  Before removal of lymphocytes, before CAR - T cells infusion, Day1, Day3, Day5, Day7, Day10, Day14, Day21, Day28, Month2, Month3, Month6, Month9, Month12, Month15, Month18, Month21, Month24

Study Arms (4)

Low Dose Group

EXPERIMENTAL

CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 0.5×10\^6 CAR+T cells/kg.

Biological: CD19-CD22 CAR-T cells

Middle Dose Group

EXPERIMENTAL

CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 2×10\^6 CAR+T cells/kg.

Biological: CD19-CD22 CAR-T cells

High Dose Group

EXPERIMENTAL

CD19-CD22 CAR-T cells injection, infused only once,3-6 subjects of low dose group will be intravenously infuse with 5×10\^6 CAR+T cells/kg.

Biological: CD19-CD22 CAR-T cells

Amplification Dose Group

EXPERIMENTAL

CD19-CD22 CAR-T cells injection, infused only once.After determined maximum tolerated dose,15 subjects of amplification dose group will be intravenously infuse with 0.5-5.0×10\^6 CAR+Tcells/kg.

Biological: CD19-CD22 CAR-T cells

Interventions

CD19-CD22 CAR-T cells BIOLOGICAL

A autologous doping CAR - T cells injection targets with CD19 and CD22，fluorine dara marina injection(30 mg/m2，QD×3d) and cyclophosphamide injection (300 mg/m2，QD×3d)will be used to remove the lymphocyte before infusion CD19-CD22 CAR-T cells .

Also known as: Fluorine dara marina injection, Cyclophosphamide injection

Amplification Dose Group; High Dose Group; Low Dose Group; Middle Dose Group

Eligibility Criteria

• Age: 6 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• year - old male or female subjects (including 6 years old and 70 years old, 6-18 subjects use only the recommended dose of treatment);
• The Clinical diagnosis of recurrent/refractory acute B lymphocytic leukemia, after at least 2 courses of treatment, has not been achieved partial response, still in the continuous phase and progress, including the MRD positive, or recurrent intramedullary patients；
• Bone marrow samples inspection by using flow cytometry or organization pathology ，the cell membrane surface antigen CD19 and/or CD22 positive；
• ECOG physical status score of 0 to 2 points;
• Expected lifetime is more than 12 weeks;
• The clinical laboratory test results of screening phase meet the following criteria: (7 days before the inspection without blood transfusion) Hb≥60 g/L (allowed to use recombinant human erythropoietin); PLT≥ 50 x 10 \^ 9 / L ; ALC≥0.3×10\^9/L; ANC≥0.75×10\^9/L (allowed to use granulocyte colony stimulating factor); AST≤3ULN,ALT≤3ULN,TBIL≤2ULN；Ccr≥30 mL/min/1.73 m2；
• Cardiopulmonary function: left ventricular ejection fraction \> 40%; Baseline blood oxygen saturation \> 95%;
• Has a history of allogeneic/allogeneic hematopoietic stem cell transplantation patients: transplantation in 3 months ago, no grade 2 or more active graft versus host disease (GVHD), more than a month without immune inhibitors.

You may not qualify if:

• The active hepatitis b, HBV - DNA detection lower limit of the subjects above research center; Hepatitis c virus (HCV) antibody positive and peripheral blood HCV - RNA positive subjects; Antibodies to HIV positive subjects; Early syphilis screening antibody positive;
• The other clinical significance of active virus, bacterial infection, or failing to control systemic fungal infection;
• Any instability of systemic disease, including but not limited to, unstable angina, cerebrovascular accident, or transient ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York heart association (NYHA) classification level III or higher congestive heart failure, drug control of serious arrhythmia, liver, kidney or metabolic diseases, as well as the standard treatment cannot control high blood pressure;
• In past two years, because of autoimmune diseases such as crohn's disease, rheumatoid arthritis and systemic lupus erythematosus (sle), etc.) causing end-organ damage, or need systemic application of immunosuppressive drugs;
• Had a history of the central nervous system diseases, such as epilepsy, serious brain damage, dementia, Parkinson's disease, psychosis,etc which influence the appraising of test,;
• Diagnosed with other active malignancy in past five years(the basal or scaly skin cancer, superficial bladder cancer, breast cancer in situ, which has been cured and does not require follow-up treatment are not included );
• Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s including accessories, DMSO ;
• Patients with pregnancy or lactation, patients do not want to take effective contraceptive measures within 6months after infusion CAR-T cells;
• The other situations that researchers determined doesn't fit to participate in this study.

Sponsors & Collaborators

• Shanxi Province Cancer Hospital: lead
• Shanghai Ultra-T Immune Therapeutics Co. LTD: collaborator

Study Sites (1)

Hematology Department of ShanXi Cancer Hospital

Taiyuan, Shanxi, 030013, China

RECRUITING

MeSH Terms

Interventions

Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Liping Su, M.D.

  Hematology Department of ShanXi Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liping Su, M.D.

CONTACT

13835158122; sulp2005@sohu.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: According to the sequence from the low dose group to the high dose group

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 19, 2021
• Study Start: January 15, 2021
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2023
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within six months after the study completed
• Access Criteria: Research site

Locations

CN (1)