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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Refractory B Acute Lymphoblastic Leukemia; Relapse B Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Second Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BLLCAR-L10D treatment group; 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.	Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment related adverse events	Assessed by CTCAE v4.0	Day 1-100 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response include complete remission and partial remission	Day 1-5 years after injection
Overall survival		Day 1-5 years after injection
Progression free survival		Day 1-5 years after injection

Other Outcome Measures

Outcome Measure	Time Frame
Copy numbers of CAR-T cells in patients	Day 1-5 years after injection

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborators: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2017
• Primary Completion (ANTICIPATED): August 30, 2020
• Study Completion (ANTICIPATED): August 30, 2020

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (ACTUAL): September 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Chimeric Antigen Receptor T cells; CD19 and CD22
• 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: XJTU-BLLCAR-L10D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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