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

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

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

Study Overview

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

Detailed Description

This is a prospective, single arm study. To evaluate the safety and efficacy of sequential CD19 and CD22 CAR-T cells in the treatment of adult newly diagnosed Ph chromosome negative B-cell acute lymphoblastic leukemia. The main endpoints were dose limiting toxicity (DLT) and incidence of adverse events (TEAEs).

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age≥15 years old
• Newly diagnosed B-cell acute lymphoblastic leukemia according to the 2016 WHO classification
• The immunophenotype of leukemia cells were CD19 and CD22 positive
• Ph- or Ph- like negative
• Anticipated survival time more than 12 weeks;
• Those who voluntarily participated in this trial and provided informed consent.

Exclusion Criteria:

• History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• Pregnant (or lactating) women;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
• Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
• Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
• Other uncontrolled diseases that were not suitable for this trial;
• Patients with HIV infection;
• Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

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
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CAR-T cells infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Complete Remission Rate	Complete Remission Rate after CAR-T cell therapy	up to 28 days after CAR-T cells infusion
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2021
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: January 31, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 5, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Newly diagnosed; B-ALL; CD19 CAR-T; CD22 CAR-T; Ph Chromosome Negative
• 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: CD19-005

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