CD19-CD22 Chimeric Antigen Receptor T (CAR-T) Cell for Treatment of B Cell Acute Lymphoblastic Leukemia (B-ALL)
Study Details
Study Description
Brief Summary
This is a single arm, open-label, single center study to determine the safety and efficacy of CD19-CD22 CAR-T cells in patients with CD19+CD22+ Leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
This is a single arm, open-label, single center study to determine the safety and efficacy of CD19-CD22 CAR-T cells in patients with relapsed or refractory B-ALL. The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from CD19-CD22 CAR-T cell infusion.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A Single dose of CD19-CD22 CAR-T cells |
Biological: CD19-CD22 CAR-T cells
0.5 to 3.0 x 106 autologous CD19-CD22 CAR-T cells per kg body weight, with a maximum dose of 4 x 108 autologous CD19-CD22 CAR-T cells via intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [24 months]
- Overall remission rate (ORR) [3 months]
Secondary Outcome Measures
- Response at Day 28 days [1 month]
- Percentage of patients who achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at month 6 without SCT between CD19-CD22 CAR-T cells infusion and Month 6 response assessment. [6 months]
- Percentage of patients who achieve CR or CRi with minimal residual disease (MRD) negative bone marrow [6 months]
- Relapse-free survival (RFS) [24 months]
- Duration of remission (DOR) [24 months]
- Overall survival (OS) [24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Informed consent is signed by a subject or his lineal relation.
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Age 3 and older.
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Documentation of cluster of differentiation 19 (CD19) and or cluster of differentiation 19 (CD22) expression on leukemic blasts in the BM, peripheral blood within 3 months of screening.;
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Relapsed or refractory B-cell ALL
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Relapse within 12 months of first remission
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Without remission after 2 cycles of induction chemotherapy regimen.
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Without remission or relapse after salvage treatments.
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Any BM relapse after autologous stem cell transplantation (ASCT).
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Without remission or relapse after any prior CD19 targeted therapy;
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Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a BCR-ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) mutation.
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Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening；
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Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
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Adequate organ function defined as:
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Aspartate aminotransferase (AST) ≤3 upper limit of normal (ULN);
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Serum alanine aminotransferase (ALT) ≤3 ULN;
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Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome;
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Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN will be eligible.
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A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min（Cockcroft and Gault）
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Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation > 91% on room air.
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Absolute lymphocyte count ≥0.3 x 10⁹/L.
- Women of child-bearing potential and all male participants must use highly effective methods of contraception for a period of 1 year after the CD19-CD22 CAR-T cells infusion.
Exclusion Criteria:
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Active central nervous system leukemia
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Patients with evidence of currently uncontrollable serious active infections (e.g., sepsis, bacteremia, fungemia, viremia, etc.).
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Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
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Major surgery within ≤ 4 weeks before enrollment.
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Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent.
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Impaired cardiac function:
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Left Ventricular Ejection Fraction (LVEF) ≤45%;
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III/IV congestive heart failure (NYHA);
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Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular tachycardia);
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Corrected QT interval (QTc) ≥450ms (male) or QTc≥470ms (female)（QTc using Bazett's formula (QTcB)=QT/RR^0.5）;
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Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery.
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Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.
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Patients with a history of epilepsy or other active central nervous system diseases.
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Life expectancy < 12 weeks.
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Allergy to macromolecule biopharmaceuticals such as antibodies or cytokines.
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Subjects who are receiving systemic steroid treatment and who have been determined by the researchers to require long-term treatment with systemic steroids during treatment, and subjects treated with systemic steroids must be excluded < 72 hours prior to CNCT19 infusion (except inhalation or local use).
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Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Hematology & Blood Diseases Hospital | Tianjin | China | 300020 |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
- Juventas Cell Therapy Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HY004001