Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T ACI Clinical Trial
Official title:
Phase I/II Study to Evaluate Treatment of Relapsed B-cell Acute Lymphoblastic Leukemia After CD19 CAR-T Adoptive Cellular Immunotherapy With CAR-T Cells Targeting CD38
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. CD38 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD38. This is a phase 1/2 study designed to determine the safety of the gene-edited specificity CD38 CAR-T cells and the feasibility of making enough to treat patients with relapsed B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy.
| Status | Recruiting |
| Enrollment | 80 |
| Est. completion date | November 23, 2022 |
| Est. primary completion date | November 23, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 12 Years to 70 Years |
| Eligibility |
Inclusion Criteria: 1. Male or female participant 2. 12 Years to 70 Years (Child, Adult, Senior) 3. Patient with relapsed CD38+ B-cell acute lymphoblastic leukemia after CD19 CAR-T adoptive cellular immunotherapy 4. Estimated life expectancy = 12 weeks (according to investigator's judgement) 5. Eastern Cooperative Oncology Group (ECOG) performance status = 1 6. Adequate organ function Exclusion Criteria: 1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease 2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis 3. Richter's syndrome 4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening 5. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy 6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible 7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening 8. Patient has an investigational medicinal product within the last 30 days prior to screening 9. Previous treatment with investigational gene or cell therapy medicine products 10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary 11. Pregnant or nursing women |
| Country | Name | City | State |
|---|---|---|---|
| China | Biotherapeutic Department and Hematology Department of Chinese PLA | Beijing | Beijing |
| Lead Sponsor | Collaborator |
|---|---|
| Chinese PLA General Hospital |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability | 24 weeks | ||
| Primary | MTD of specificity CD38 CAR-T cells | The highest dose of specificity CD38 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of specificity CD38 CAR-T cells. | 4 weeks | |
| Primary | Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes | 24 weeks | ||
| Secondary | Six-month Objective response rate of complete remission and partial remission | 24 weeks | ||
| Secondary | Six-month Overall survival | 24 weeks | ||
| Secondary | Six-month Progression free survival | 24 weeks |