Sequential CD19 and CD22 CAR-T Therapy for Newly Diagnosed Ph+ B-ALL

Clinical Trial for the Efficacy and Safety of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients with Newly Diagnosed Ph Chromosome Positive B-cell Acute Lymphoblastic Leukemia

Clinical Trial for the Efficacy and Safety of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients With Newly Diagnosed Ph Chromosome Positive B-cell Acute Lymphoblastic Leukemia

Study Overview

• Status: Completed
• Conditions: B-Cell Acute Lymphoblastic Leukemia, Adult
• Intervention / Treatment: Drug: CAR-T cells targeting CD19 and CD22

Detailed Description

This study was designed as a prospective, open-label, single-center study. It aims to evaluate the efficacy and safety of CD19 CAR-T cells in combination with dasatinib for the treatment of newly diagnosed Ph-positive B-cell acute lymphoblastic leukemia in adult.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old;
2. Subjects with a diagnosis of B-cell acute lymphoblastic leukemia according to the 2016 edition of the WHO classification criteria for acute leukemia;
3. Subjects whose chromosomal and fusion gene analysis showed positivity for the Ph chromosome, BCR/ABL1 fusion gene;
4. Leukemia cells were CD19 and CD22 positive;
5. Patients with newly diagnosed B-ALL were not treated with standard chemotherapy regimens;
6. Serum total bilirubin ≤ 51 mol/L, serum ALT and AST both ≤ 3 times the upper limit of the normal range, blood creatinine ≤ 176.8 mol/L;
7. Echocardiography showed a left ventricular ejection fraction (LVEF) ≥50%;
8. Subjects had no active pulmonary infection and oxygen saturation ≥92% without oxygen;
9. The prognosis for survival is more than 3 months;
10. ECOG score 0-2;
11. Subjects volunteered to participate in this trial and signed an informed consent form.

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for enrollment in this trial:

1. Those with a history of epilepsy or other central nervous system disorders;
2. Those with a history of prolonged QT period or severe cardiac disease;
3. Women who are pregnant or breastfeeding (the safety of this therapy for the unborn child is not known);
4. Those with uncontrolled active infection;
5. Active hepatitis B or hepatitis C virus infection;
6. Those who have previously used any gene therapy product;
7. Those with insufficient amplification (<5-fold) in response to CD3/CD28 co-stimulatory signals;
8. Creatinine > 2.5 mg/dl or ALT / AST > 3 times the upper limit of the normal range or bilirubin > 2.0 mg/dl;
9. Those who suffer from other uncontrolled medical conditions that, in the opinion of the investigator, make them unsuitable for enrollment;
10. HIV-infected persons;
11. Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T therapy; Administration of CD19 and CD22 CAR T-cells	Drug: CAR-T cells targeting CD19 and CD22; Each subject receives sequential CD19 and CD22 CAR-T cells by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete molecular response (CMR) rate	Complete molecular response (CMR) rate after CD19 CAR-T cell therapy	Up to 1 month after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	From the first infusion of CD19 CAR-T cells to death or the last visit	Up to 2 years after CD19 CAR-T cells infusion
Leukemia-free survival (LFS)	From the complete remission to the occurrence of any event, including death, relapse (any one occurs first), and the last visit	Up to 2 years after CD19 CAR-T cells infusion
Complete molecular response (CMR) rate	Complete molecular response (CMR) rate after CD22 CAR-T cell therapy	Up to 1 month after CAR-T cells infusion
cumulative incidence of relapse (CIR)	From the complete remission to relapse	Up to 2 years after CD19 CAR-T cells infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events (Safety and Tolerability)	Through study completion, an average of 2 years
Characterization of relapse	Including expression of CD19, CD22 and mutations in the ABL1 gene	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Actual): August 31, 2024
• Study Completion (Actual): August 31, 2024

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Newly diagnosed; B-ALL; CD19 CAR-T; CD22 CAR-T; Ph Chromosome Positive
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: CD19-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No