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Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia

Primary Purpose

Refractory B Acute Lymphoblastic Leukemia, Relapse B Acute Lymphoblastic Leukemia

Status
Withdrawn
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy
Sponsored by
Second Affiliated Hospital of Xi'an Jiaotong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory B Acute Lymphoblastic Leukemia focused on measuring Chimeric Antigen Receptor T cells, CD19 and CD22

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent could be acquired;
  2. Diagnosed with relapse/refractory acute lymphoblastic leukemia;
  3. Relapse was defined as recurrence of blast cell(more than 5%) in peripheral blood or in bone marrow or extramedullary involvement;
  4. Refractory was defined as failed to achieve complete remission after two courses of induction therapy;
  5. CD19/CD22 postive leukemia cell was confirmed by flow cytometry or immunohistochemistry within 90 days since enrollment in this trial;
  6. Karnofsky score ≥70;
  7. Results of pregnant test should be negative, and agree to conception control during treatment and 6 months after CAR-T infusion.
  8. Adequate organ function: EF≥50%; normal ECG; CCR ≥ 50ml/min or Cr < 2.0mg/dL or < 2 times upper limitation of normal; ALT and AST<5 times upper limitation of normal; Serum bilirubin ≤ 3.0mg/dL; DLCO or FEV1 > 45% of predict value;
  9. At least 2 weeks intervals since the last chemotherapy;
  10. At least 2 weeks intervals since the last anti-GVHD therapy if patients have ever ;

Exclusion Criteria:

  1. Patients diagnosed with acute promyelocytic leukemia:t(15;17)(q22;q12);
  2. Women in pregnancy and lactation;
  3. Uncontrolled infection, Active HBV or HCV infection, HIV positive or any other deadly bacterial/virual diseases;
  4. Long term use of systemic corticosteroids(5mg per day for 2 weeks);
  5. Any other uncontrolled life-threaten diseases;
  6. Patients with history of anaphylaxis to any drugs;
  7. With central nervous system (CNS) involvement;
  8. Patients with GVHD after allo-HSCT who needed immunosuppressive agents ;
  9. Patients with acute autoimmune diseases such as psoriasis or rheumatoid arthritis;
  10. Other conditions that principle investigator considered may increase the risk of the patients or interference the results.

Sites / Locations

  • Second Affiliated Hospital of Xi'an Jiaotong University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BLLCAR-L10D treatment group

Arm Description

In BLLCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10^6, 1.5×10^6, 2.0×10^6 CAR-T cells/kg.

Outcomes

Primary Outcome Measures

Occurrence of treatment related adverse events
Assessed by CTCAE v4.0

Secondary Outcome Measures

Objective response rate
Objective response include complete remission and partial remission
Overall survival
Progression free survival

Full Information

First Posted
September 17, 2019
Last Updated
November 3, 2020
Sponsor
Second Affiliated Hospital of Xi'an Jiaotong University
Collaborators
Nanjing Legend Biotech Co.
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1. Study Identification

Unique Protocol Identification Number
NCT04094766
Brief Title
Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia
Official Title
A Phase I Clinical Study of Dual Specificity CD19 and CD22 Chimeric Antigen Receptor T Cell Therapy in Relapsed or Refractory Acute B Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Production plan adjustment
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
August 30, 2020 (Anticipated)
Study Completion Date
August 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Xi'an Jiaotong University
Collaborators
Nanjing Legend Biotech Co.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of dual specificity CD19 and CD22 CAR-T cells in patients with relapsed and refractory acute B lymphoblastic leukemia.
Detailed Description
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory acute B lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual specificity CAR enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory B Acute Lymphoblastic Leukemia, Relapse B Acute Lymphoblastic Leukemia
Keywords
Chimeric Antigen Receptor T cells, CD19 and CD22

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BLLCAR-L10D treatment group
Arm Type
Experimental
Arm Description
In BLLCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10^6, 1.5×10^6, 2.0×10^6 CAR-T cells/kg.
Intervention Type
Drug
Intervention Name(s)
Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy
Intervention Description
Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.
Primary Outcome Measure Information:
Title
Occurrence of treatment related adverse events
Description
Assessed by CTCAE v4.0
Time Frame
Day 1-100 days after injection
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Objective response include complete remission and partial remission
Time Frame
Day 1-5 years after injection
Title
Overall survival
Time Frame
Day 1-5 years after injection
Title
Progression free survival
Time Frame
Day 1-5 years after injection
Other Pre-specified Outcome Measures:
Title
Copy numbers of CAR-T cells in patients
Time Frame
Day 1-5 years after injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent could be acquired; Diagnosed with relapse/refractory acute lymphoblastic leukemia; Relapse was defined as recurrence of blast cell(more than 5%) in peripheral blood or in bone marrow or extramedullary involvement; Refractory was defined as failed to achieve complete remission after two courses of induction therapy; CD19/CD22 postive leukemia cell was confirmed by flow cytometry or immunohistochemistry within 90 days since enrollment in this trial; Karnofsky score ≥70; Results of pregnant test should be negative, and agree to conception control during treatment and 6 months after CAR-T infusion. Adequate organ function: EF≥50%; normal ECG; CCR ≥ 50ml/min or Cr < 2.0mg/dL or < 2 times upper limitation of normal; ALT and AST<5 times upper limitation of normal; Serum bilirubin ≤ 3.0mg/dL; DLCO or FEV1 > 45% of predict value; At least 2 weeks intervals since the last chemotherapy; At least 2 weeks intervals since the last anti-GVHD therapy if patients have ever ; Exclusion Criteria: Patients diagnosed with acute promyelocytic leukemia:t(15;17)(q22;q12); Women in pregnancy and lactation; Uncontrolled infection, Active HBV or HCV infection, HIV positive or any other deadly bacterial/virual diseases; Long term use of systemic corticosteroids(5mg per day for 2 weeks); Any other uncontrolled life-threaten diseases; Patients with history of anaphylaxis to any drugs; With central nervous system (CNS) involvement; Patients with GVHD after allo-HSCT who needed immunosuppressive agents ; Patients with acute autoimmune diseases such as psoriasis or rheumatoid arthritis; Other conditions that principle investigator considered may increase the risk of the patients or interference the results.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aili He, MD, PhD
Organizational Affiliation
Second Affiliated Hospital of Xi'an Jiaotong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Second Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia

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