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

Study Overview
=================
Brief Summary
-----------------
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

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

Official Title
-----------------
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

Conditions
-----------------
Ph Positive ALL, CAR-T Cell, Dasatinib

Intervention / Treatment
-----------------
* Drug: Dasatinib plus anti-CD19/CD22 CAR-T cells


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Creatinine is in the normal range; Left ventricular ejection fraction >50%; Baseline oxygen saturation>92%; Total bilirubin ≤ 1.5×ULN; 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 Ultrasound shows left ventricular ejection fraction <50%; stable/unstable angina,myocardia infarction Baseline oxygen saturation>92%; history of pacemaker inplantation more than 2 leads ST segments decrease>1mm,or more than 2 consecutive leads T wave inversion; Long QT syndrom A severe arrhythmia requiring medical treatments 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

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention 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<br>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<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD19/CD22 Bispecific CAR-T, Ph-positive lymphoblastic leukemia, Dasatinib