Combining Dasatinib with Bispecific CAR-T Therapy for Elderly Patients with Ph-positive ALL

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

This study is testing if combining a drug called Dasatinib with a special CAR-T cell therapy can help older patients with a type of leukemia called Ph-positive acute lymphoblastic leukemia feel better and have better treatment results.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 55 Years to 70 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: Dasatinib, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai)
• Trial ID: NCT05523661 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of combining Dasatinib with CD19/CD22 Bispecific CAR-T cell therapy for elderly patients diagnosed with Ph-positive acute lymphoblastic leukemia (ALL). Patients aged 55 to 70 will receive Dasatinib along with VP chemotherapy for induction treatment. If they achieve a hematologic complete remission, they will undergo lymphocyte collection followed by a chemotherapy regimen of fludarabine and cyclophosphamide, culminating in a single infusion of CAR-T cells. The study aims to improve treatment outcomes for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed Ph-positive ALL patients aged 55 to 70 with an ECOG score of 0-1.

Not a fit: Patients with disease relapse or other malignant tumors within the past five years may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new effective treatment option for elderly patients with Ph-positive ALL.

How similar studies have performed: While CAR-T therapies have shown promise in various hematological malignancies, this specific combination approach is novel and has not been extensively tested in this patient demographic.

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:

  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

Where this trial is running

Shanghai

• Shanghai General Hospital — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song, M.D. — Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Xianmin Song, M.D.

Conditions Ph Positive ALL; CAR-T Cell; Dasatinib; CD19/CD22 Bispecific CAR-T; Ph-positive lymphoblastic leukemia