Dasatinib Plus Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for Elderly Ph-positive ALL Patients

November 26, 2023 updated by: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

The Safety and Clinical Efficacy of Dasatinib Plus Human CD19/CD22 Bispecific CAR-T Cell Therapy for Elderly Subjects With Ph-positive Acute Lymphoblastic Leukemia

To evaluate the safety and efficacy of Dasatinib plus CD19/CD22 Bispecific CAR-T for the treatment of elderly Ph-positive lymphoblastic leukemia. Newly diagnosed Ph-positive patients will be given Dasatinib plus VP chemotherapy for induction treatment,if a hematologic complete remission was observed then a lymphocyte collection will be administrated to patients. Then chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Newly diagnosed ph-positive ALL patients over 60 and less than 70 years old will be enrolled. Patients will be given Dasatinib plus VP chemotherapy for induction remission treatment, if a hematologic complete remission was observed then a lymphocyte collection will be administrated to patients. Then chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Xianmin Song, M.D.
  • Phone Number: 021-63240090
  • Email: shongxm@139.com

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

51 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • (1)55 to 70 Years Old, Male and female;
  • (2) Newly diagnosed Ph-positive ALL
  • (3) ECOG score 0-1;
  • (4) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;

  • (5) Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Creatinine is in the normal range;
    2. Left ventricular ejection fraction >50%;
    3. Baseline oxygen saturation>92%;
    4. Total bilirubin ≤ 1.5×ULN;
    5. ALT and AST ≤ 2.5×ULN;
  • (6) Able to understand and sign the Informed Consent Document

Exclusion Criteria:

  • (1) Disease relapse;
  • (2) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
  • （3) ECOG >=2 during CAR-T therapy

  • (4) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Heart disease including the following condition

    1. Ultrasound shows left ventricular ejection fraction <50%;
    2. stable/unstable angina,myocardia infarction
    3. Baseline oxygen saturation>92%;
    4. history of pacemaker inplantation
    5. more than 2 leads ST segments decrease>1mm,or more than 2 consecutive leads T wave inversion;
    6. Long QT syndrom
    7. A severe arrhythmia requiring medical treatments
    8. bradycardia,HR<50BPM I.QTc>450ms
  • (5)Uncontrolled infection during screening peroid; Hemodynamic instability associated with infection,a new infection or aggravation of the original infection;new lesions on imaging;fever of unkown cause
  • (6) Patients with symptoms of central nervous system;greater than grade 2 requring treatment,paralysis,aphasia,acute cerebral infarction,severe traumatic brain injury,schizophrenia
  • (7)Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
  • (8) HIV infection
  • (9)Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
  • (10) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
  • (11) allergy to Dasatinib
  • (12) history of autoimmune disaese

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dasatinib plus anti-CD19/CD22 CAR-T cells
Administration with oral Dasatinib plus anti-CD19/ CD22 CAR-T cells in the elderly Ph-positive ALL patients.
Drug: Dasatinib plus anti-CD19/CD22 CAR-T cells
Dasatinib plus VP chemotherapy was administrated to newly diagnosed Ph-positive patients aged 55-70 years old,if hCR was achieved,autolymphocyte was collected,and anti-CD19/CD22 CAR-T cells infusion was administrated to patients followed by Fludarabine and Cyclophosphamide therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients achieving molecular CR
Time Frame: 3 months after infusion of Anti-CD19/CD22 CAR-T cells
number of patients achieving molecular CR
3 months after infusion of Anti-CD19/CD22 CAR-T cells

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS for patients receiving infusion of anti-CD19/CD22 CAR-T cells
Time Frame: 2-year OS
Overall survival for all patients enrolled
2-year OS
RFS for patients receiving infusion of anti-CD19/CD22 CAR-T cells
Time Frame: 2-year RFS
Relapse free survival for all patients enrolled
2-year RFS
Number of patients achieving molecular CR
Time Frame: 6 months after infusion of Anti-CD19/CD22 CAR-T cells
number of patients achieving molecular CR after infusion of Anti-CD19/CD22 CAR-T cells
6 months after infusion of Anti-CD19/CD22 CAR-T cells

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

  • Principal Investigator: Xianmin Song, M.D., Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

November 14, 2021

First Submitted That Met QC Criteria

August 29, 2022

First Posted (Actual)

August 31, 2022

Study Record Updates

Last Update Posted (Actual)

November 28, 2023

Last Update Submitted That Met QC Criteria

November 26, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HRAIN01-ALL02-POC

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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