The goal of this clinical trial is to evaluate the safety, tolerability, and preliminary efficacy in adult patients with relapsed or refractory (r/r) CD19-positive B-cell Non-Hodgkin Lymphoma (B-NHL) or B-cell Leukemia. The main questions it aims to answer are: * What are the safety and tolerability profiles of GI001, specifically regarding the incidence of Dose-Limiting Toxicities (DLTs) and the determination of the Maximum Tolerated Dose (MTD)? * What is the preliminary efficacy of GI001, measured by Objective Response Rate (ORR), Complete Response Rate (CRR), and Duration of Response (DOR)? * What are the pharmacokinetic (expansion and persistence of CAR-T cells) and pharmacodynamic (cytokine changes) characteristics of GI001? Participants will: * Undergo a screening process (D-30 to D-3) and baseline evaluation to ensure eligibility, including confirmation of CD19-positive disease. * Receive a single intravenous infusion of GI001 at one of four designated dose levels (1E8, 3E8, 7E8 or 1E9 TU) following an "Accelerated Titration" and "3+3" dose-escalation design. * Remain hospitalized for at least 14 days post-infusion for intensive safety monitoring, specifically for Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). * Provide multiple blood, saliva, and urine samples for pharmacokinetic (PK), pharmacodynamic (PD), and exploratory analysis (including immunogenicity and viral shedding). * Participate in efficacy and safety follow-ups through Month 24, followed by a long-term safety follow-up for up to 15 years.
Study Design and Methodology This is an investigator-initiated, open-label, single-arm, dose-escalation, and expansion exploratory clinical study. The study utilizes an "Accelerated Titration" combined with a standard "3+3" design to evaluate the safety, tolerability, and preliminary anti-tumor activity of GI001 injection-an innovative in vivo CAR-T therapy-in patients with relapsed or refractory (r/r) CD19+ B-cell malignancies. Dose Escalation Phase Four dose levels have been pre-specified: 1E8, 3E8, 7E8 or 1E9 TU 1. Accelerated Titration: The first subject will be enrolled at the starting dose ( TU). If no Dose-Limiting Toxicity (DLT) or Grade 2 treatment-related adverse events occur within the 28-day DLT observation period, the study may proceed to the next dose level with a single subject. 2. Standard 3+3 Design: If a DLT or significant toxicity (as defined in the protocol) is observed during the accelerated phase, the study will transition to a traditional 3+3 escalation model to ensure subject safety and more robustly determine the Maximum Tolerated Dose (MTD). Dose Expansion Phase Upon completion of the escalation phase and determination of the MTD or Recommended Dose for Expansion (RDE), an additional 12-18 subjects will be enrolled to further characterize the safety profile and provide a more comprehensive assessment of preliminary efficacy. Treatment and Monitoring Subjects will receive a single intravenous infusion of GI001. Due to the risk of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), subjects must be hospitalized for intensive monitoring for at least 14 days post-infusion. Clinical assessments, including physical examinations, vital signs, and laboratory tests (hematology, biochemistry, and coagulation), will be conducted at frequent intervals. Pharmacokinetics (PK) and Pharmacodynamics (PD) A central laboratory will analyze peripheral blood, saliva, and urine samples to: * Quantify the expansion and persistence of GI001 CAR-T cells using qPCR and/or Flow Cytometry. * Monitor systemic cytokine levels (e.g., IL-6, IFN-, TNF-) to correlate with safety and efficacy outcomes. * Assess immunogenicity (Anti-Drug Antibodies) and potential viral shedding (RCL testing) to ensure long-term biological safety. Long-Term Follow-up Following the initial 24-month efficacy and safety evaluation period, subjects will be invited to participate in a long-term safety follow-up study for up to 15 years, in accordance with regulatory guidelines for gene therapy products, to monitor for delayed adverse events such as secondary malignancies or prolonged B-cell aplasia.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Biological: GI001 Injection GI001 is an innovative chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19-positive B-cell malignancies. Administration: Subjects will receive a single dose of GI001 via intravenous (IV) infusion on Day 0. Dosing Logic: The study follows a dose-escalation design with four pre-specified dose levels: 1E8, 3E8, 7E8, and 1E9 Transducing Units (TU). The dosage is determined based on the total TU count as measured by flow cytometry. Pre-medication: Prior to infusion, subjects may receive pre-conditioning (lymphodepletion chemotherapy) as per protocol and prophylactic medication (e.g., promethazine or diphenhydramine) to prevent infusion reactions.
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
* Title: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) * Description: Adverse events will be assessed and graded according to NCI CTCAE v6.0 for general toxicities. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) will be graded according to ASTCT 2019 criteria. This measure reports the number of participants experiencing these events.
Time frame: Baseline up to 24 months post-infusion
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLTs are defined as specific severe toxicities occurring within the DLT observation period. This measure is used to evaluate safety, determine the Maximum Tolerated Dose (MTD), and identify the Recommended Dose for Expansion (RDE).
Time frame: D0 up to D28
Number of Participants with Clinically Significant Changes in Vital Signs
This measure reports the number of participants experiencing clinically significant abnormal changes from baseline in vital signs, including systolic/diastolic blood pressure, heart rate, respiratory rate, or body temperature.
Time frame: Baseline up to 24 months post-infusion
Number of Participants with Clinical Laboratory Abnormalities
This measure reports the number of participants experiencing clinically significant laboratory abnormalities or Grade 3/4 toxicities (assessed via hematology, serum chemistry, coagulation, and urinalysis) from baseline.
Time frame: Baseline up to 24 months post-infusion
Number of Participants with Clinically Significant Abnormal Physical Examination Findings
The number of participants who develop new, clinically significant abnormal findings during physical examinations compared to baseline.
Time frame: Baseline up to 24 months post-infusion
Changes in 12-Lead Electrocardiogram (ECG) Parameters from Baseline
Includes changes in heart rate, PR interval, QRS duration, and QTcF interval from baseline to assess cardiac safety.
Time frame: Baseline up to 24 months post-infusion
Changes in Eastern Cooperative Oncology Group (ECOG) Performance Status Score from Baseline
The ECOG performance status scale ranges from 0 (fully active) to 5 (dead). Higher scores indicate worse performance status. The change in score from baseline will be reported.
Time frame: Baseline up to 24 months post-infusion
Objective Response Rate (ORR)
The proportion of participants achieving a Complete Response (CR) or Partial Response (PR). For B-NHL, tumor response is assessed per Lugano 2014 criteria; for B-ALL, response is defined according to protocol-specified clinical criteria.
Time frame: D0 up to 24 months post-infusion
Complete Response Rate (CRR)
The proportion of participants achieving a Complete Response (CR) as their best overall response.
Time frame: D0 up to 24 months post-infusion
Duration of Response (DOR) in Months
Defined as the time from the first documented disease response (CR or PR) to the date of first documented disease progression or death from any cause.Reported in months.
Time frame: D0 up to 24 months post-infusion
Progression-Free Survival (PFS)
Defined as the time from the date of first study drug infusion to the date of first documented disease progression or death from any cause.
Time frame: D0 up to 24 months post-infusion
Overall Survival (OS)
Defined as the time from the date of first study drug infusion to the date of death from any cause.
Time frame: D0 up to 24 months post-infusion
Minimal Residual Disease (MRD) Negativity Rate
The proportion of participants achieving MRD negativity as determined by highly sensitive detection methods (applicable primarily for B-ALL participants).
Time frame: D0 up to 24 months post-infusion
Peak Concentration (Cmax) of CAR-T Cells and CAR Copies
The maximum observed concentration of CD19 CAR-T cells and CAR copy numbers in peripheral blood following GI001 infusion.
Time frame: Baseline, and multiple time points up to Day 28"
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Time to Peak Concentration (Tmax) of CAR-T Cells
The time required to reach the maximum observed concentration (Cmax) of CD19 CAR-T cells and CAR copy numbers in peripheral blood following GI001 infusion.
Time frame: Baseline, and multiple time points up to Day 28"
Area Under the Curve from Day 0 to Day 28 (AUC 0-28d)
The area under the concentration-time curve from the time of GI001 infusion (Day 0) to Day 28 for CD19 CAR-T cells and CAR copy numbers in peripheral blood.
Time frame: Baseline, and multiple time points up to Day 28"
Changes in Serum Cytokine Concentrations from Baseline
ncludes changes in levels of systemic inflammatory markers such as IL-2, IL-6, IL-10, IFN-γ, and TNF-α from baseline to evaluate the pharmacodynamic activity and biological impact of the CAR-T treatment.
Time frame: Baseline, and multiple time points through 6 months post-infusion
Changes in Serum C-Reactive Protein (CRP) Levels from Baseline
Measurement of changes in serum CRP levels from baseline to monitor systemic inflammatory response.
Time frame: Baseline, and multiple time points through 6 months post-infusion
Changes in Serum Ferritin Levels from Baseline
Measurement of changes in serum ferritin levels from baseline to monitor systemic inflammatory response.
Time frame: Baseline, and multiple time points through 6 months post-infusion
Changes in Peripheral Blood Lymphocyte Subset Counts from Baseline
Includes changes in the absolute cell counts of CD19+ B cells, CD3+ T cells, CD4+ T cells, and CD8+ T cells from baseline to evaluate immune cell profiles.
Time frame: Baseline, and multiple time points through 6 months post-infusion
Changes in CD4/CD8 T-Cell Ratio from Baseline
Measurement of changes in the ratio of CD4+ T cells to CD8+ T cells in peripheral blood from baseline.
Time frame: Baseline, and multiple time points through 6 months post-infusion