Evaluation of GI001 for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
ConditionB-Cell Non-Hodgkin Lymphoma
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRuijin Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: 18 years and older (inclusive).
Histopathological diagnosis includes: indolent lymphoma (iNHL), including but not limited to follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL), hairy cell leukemia (HCL), etc.; aggressive B-cell lymphoma, including but not limited to diffuse large B-cell lymphoma (DLBCL, including Richter-transformed DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), lymphoblastic lymphoma (LBL), transformed follicular lymphoma (TFL), and T-cell/histiocyte-rich large B-cell lymphoma (TCRBCL), etc., and patients in the lymphoma leukemia phase involving the bone marrow.
Definition of refractory: Best response to first-line standard therapy is PD; or response to first-line therapy is SD for 6 months after at least 4 cycles; or no response to second-line or later therapies, including PD as best response to the most recent therapy; or SD for 6 months after at least 2 cycles of the most recent therapy; or disease progression or biopsy-confirmed relapse within 12 months after autologous hematopoietic stem cell transplantation (ASCT); or patients undergoing salvage therapy after ASCT with no remission or relapse (SD or PD) after the last treatment; or relapse more than 3 months after CAR-T cell therapy in CD19+ patients.
Definition of relapse: PD again after achieving remission (including PR or CR) following adequate treatment.
Disqualifiers
Cytotoxic chemotherapy within 2 weeks before administration.
Small molecule targeted therapy within 2 weeks before administration.
Antibody therapy within 3 weeks before administration.
PEG-asparaginase within 4 weeks before administration.
Trial design
Design model
Single group
Treatments tested in this trial
GI001 Injection
Biological/VaccineBiological: 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.
Treatment groups
9 Participants
are divided into 1 treatment groupGroup A: GI001 Experimental GroupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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-infusion2
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 D283
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-infusion4
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-infusionSecondary outcomes
1
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-infusion2
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-infusion3
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-infusion4
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-infusionLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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