CD19+ Relapse/Refractory B-ALL
Conditions
Keywords
B-ALL, CAR-T
Brief summary
This is a single-arm, open-label phase I study to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19 cells for patients with CD19+ relapse/refractory B-ALL under the age of 25.
Detailed description
B-cell acute lymphoblastic leukemia (B-ALL) accounting for 85% of all ALL cases, is a common hematological malignancy in children and adults. CD19 is a widely expressed antigen in both normal B cells and B cells-derived leukemia and lymphomas. This is a single-arm, open-label phase I study of CAR-T-19 (anti CD19 scFv chimeric antigen receptor T) cells for patients with CD19-positive relapse/refractory B-ALL under the age of 25. Primary endpoint is to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19. Secondary endpoints measure ORR, OS and others.
Interventions
BIOLOGICALCAR-T-19 Cells
T cells were isolated from the PBMC of patients, transduced with lentivirus, expanded in vitro, and infused into patients. The escalated doses include 0.5×10\^6/kg,1.5×10\^6/kg, 5.0×10\^6/kg CAR+ cells.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
* Patients with relapse/refractory B-ALL. * Tumor cells from bone marrow or peripheral blood are measured CD19+ with 3 months before enrollment. * Karnofsky Score ≥ 70 or Lansky Score ≥ 50. * Patients who have a life expectancy of at least 12 weeks. * Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures.
Exclusion criteria
* Patients with extramedullary relapse (EMR). * Patients with genetic diseases, Burkitt lymphoma and leukemia or other malignancies. * Patients positive for any of the following: HbsAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA. * Patients with other uncontrolled infection. * Patients who received anti-CD19 / anti-CD3 therapy, or any other anti-CD19 therapy. * Patients with active Grade II-IV GVHD within 3 months prior to screening. * Tumor cells are detected in cerebrospinal fluid. * Patients who received HSCT within 3 months prior to screening. * Anticipated other clinical trials within 4 weeks before this trial * Pregnant or lactating women. * Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | up to 2 years | DLT within 28 days (±3 days) after CAR-T-19 infusion. |
| Maximum tolerated dose (MTD) | up to 2 years | The maximum dose of DLT occurred in ≤1/6 of the subjects within 28 days (±3 days) after CAR-T-19 infusion. |
| Adverse events | up to 2 years | Percentage of subjects with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | up to 2 years | The time from CAR-T-19 infusion to recurrence, progression or death from any cause, whichever occurs first. |
| Overall recovery rate (ORR) | up to 2 years | Percentage of subjects who achieved complete response (CR) and incomplete hematologic recovery (CRi) for the first time at Day 28 and Day 90 after CAR-T-19 infusion. |
| Overall survival (OS) | up to 2 years | The time from CAR-T-19 infusion to death from any cause. |
| MRD-Negative Rate | up to 2 years | Percentage of subjects with MRD-negative CR and incomplete blood and MRD-negative CRi for the first time at Day 28 and Day 90 after CAR-T-19 infusion. |
| Duration of Response (DOR) | up to 2 years | The time from achieving CR and CRi for the first time to recurrence or death from any cause |
Countries
China
Contacts
Primary ContactDaihong Liu
Outcome results
None listed