U96-CAR-T-Cells For R/R B-ALL
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe First Affiliated Hospital of Soochow University
About this trial
This study is a single-arm, open-label clinical investigation to evaluate the tolerance, safety and preliminary efficacy of CAR-T (U96) in the treatment of relapsed/refractory B-cell tumors. The study will be conducted in two disease types, acute B-lymphoblastic leukemia and B-cell lymphoma, with a dose escalation plan using the "3+3" method. Each dose group is planned to enroll 3 to 6 patients, with a total of approximately 30 to 48 patients to be enrolled in the entire study. After signing the informed consent form, patients will undergo screening tests. If they meet the inclusion and exclusion criteria, they will be enrolled in the study. After receiving U96 treatment, patients will be followed up. It is recommended that they stay in the hospital for at least 14 days after administration. Safety and efficacy follow-ups will be conducted at 28 days and 3, 6, 12, 18, and 24 months after treatment. The follow-up period after treatment will last for 2 years, with a long-term follow-up of 15 years to assess the efficacy and safety until the end of the study or the patient withdraws from the study. For patients who have received U96 treatment, even if they withdraw from the study early, the investigators should still conduct long-term safety follow-ups according to the protocol to evaluate the long-term safety of the product.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
(All the following items must be met simultaneously)
Patients must voluntarily sign the informed consent form and have good compliance;
The age at signing the informed consent form is ≥ 18 years old, both male and female are acceptable;
According to the standards of the National Comprehensive Cancer Network (NCCN) Acute Lymphoblastic Leukemia Clinical Practice Guidelines (2024, 2nd Edition), it is clearly diagnosed as acute B lymphoblastic leukemia;
Disqualifiers
(Any of the following conditions will disqualify one from participating)
Having another malignant tumor and the investigator considers that the presence of other malignant tumors may affect the current treatment;
Any of the following conditions: positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is greater than the minimum detection limit; positive for hepatitis C antibody (HCV-Ab), and the HCV-RNA copy number is greater than the minimum detection limit; positive for anti-mycoplasma antibody (TP-Ab); positive for human immunodeficiency virus (HIV) antibody;
Existing bacterial, fungal, viral, mycoplasma or other types of infections and the investigator determines that they are difficult to control;
Trial design
Design model
Sequential
Treatments tested in this trial
U96
DrugU96(CD7-targeted lentiviral vector for in vivo production of IL-6 knockdown CD19 CAR)
Treatment groups
30 Participants
are divided into 8 treatment groups8
Treatment groupsSee each treatment group below.
Group A: Acute B lymphocytic leukemia group1Experimental treatment 1 intervention
Group B: Acute B lymphocytic leukemia group2Experimental treatment 1 intervention
Group C: Acute B lymphocytic leukemia group3Experimental treatment 1 intervention
Group D: Acute B lymphocytic leukemia group4Experimental treatment 1 intervention
Group E: B-cell lymphoma group1Experimental treatment 1 intervention
Group F: B-cell lymphoma group2Experimental treatment 1 intervention
Group G: B-cell lymphoma group3Experimental treatment 1 intervention
Group H: B-cell lymphoma group4Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-limiting toxicity (DLT)
Description: DLT refers to any of the following conditions occurring within 28 days after cell reinfusion that are related to cell infusion: ① Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) not caused by the underlying disease and taking more than 30 days to resolve to ≤ Grade 2. ② Non-hematologic DLT: Any toxicity ≥ Grade 4 that is possibly related to CAR-T therapy, or Grade 3 toxicity that requires ≥7 days to resolve to ≤ Grade 2 or to return to baseline.
Time frame
Within 28 days after U96 infusion2
Adverse Event (AE）
Description: Record the types, occurrence frequency and severity of adverse events (AEs) related to CAR-T, with specific definitions determined according to CTCAE v5.0.The CRS and ICANS ratings do not use CTCAE but adopt the evaluation criteria in the ASTCT standards.
Time frame
2 yearsSecondary outcomes
1
Objective Response Rate (ORR)
The acute B lymphocytic leukemia group is defined as the proportion of patients who achieved complete remission (CR), complete remission with incomplete hematological recovery (CRh), and complete remission with incomplete bone marrow recovery (CRi); the B-cell lymphoma group is defined as the complete remission rate (CR) and partial remission (PR) as determined by the investigators.
Time frame
28 days and within 3 months after infusion of U962
MRD-negative rate (for B-ALL)
The proportion of B-ALL patients with negative MRD in the bone marrow when the therapeutic effect reaches remission. B-ALL patients have residual leukemia cells in the bone marrow detected by flow cytometry below 10-⁴ and/or negative qualitative or quantitative detection of bone marrow fusion genes (if any).MRD is detected by CD19 flow cytometry immunophenotyping (bone marrow).
Time frame
28 days and within 3 months after infusion of U963
Duration of Response (DOR)
It refers to the time from the evaluation of CR/CRh/CRi in patients with acute B-cell leukemia, or from the time when patients with B-cell lymphoma first reach response (CR or PR) to disease recurrence/disease progression/death due to disease.Subjects who have not experienced disease progression or death by the time of the final data collection will be censored at the time of their last valid tumor assessment. Common reasons for censoring include, but are not limited to: ①Loss to follow-up; ②Withdrawal from the study; ③Initiation of a new anticancer therapy.
Time frame
2 years4
Best Overall Response (BOR)
The Best Overall Response is defined as the proportion of patients who achieve the best response (CR or CRi) after study treatment.The review period extends from the start of infusion of U96 until the initiation of subsequent anti-cancer therapy, disease progression, withdrawal of consent, death, or study closure, whichever comes first.
Time frame
2 yearsSponsors and contacts
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Source ClinicalTrials.gov
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