Evaluation of GI001 for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT07584850 | Not Yet Recruiting Early Phase 1

• 1 other identifier: GI001-02
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (7)

• 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.

  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).

  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.

  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.

  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.

  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.

  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.

  Baseline up to 24 months post-infusion

Secondary Outcomes (14)

• Objective Response Rate (ORR)

  D0 up to 24 months post-infusion

• Complete Response Rate (CRR)

  D0 up to 24 months post-infusion

• Duration of Response (DOR) in Months

  D0 up to 24 months post-infusion

• Progression-Free Survival (PFS)

  D0 up to 24 months post-infusion

• Overall Survival (OS)

  D0 up to 24 months post-infusion

Study Arms (1)

GI001 Experimental Group

EXPERIMENTAL

Patients with relapsed or refractory CD19-positive B-cell malignancies receiving a single intravenous infusion of GI001. The study includes a dose-escalation phase ( 1E8 to 1E9 TU) and a subsequent expansion phase at the recommended dose.

Biological: GI001 Injection

Interventions

GI001 Injection BIOLOGICAL

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.

GI001 Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 years and older (inclusive).
• Diagnosis: Diagnosis of CD19-positive relapsed/refractory B-cell lymphoma/leukemia:
• \) CD19-positive relapsed or refractory B-cell lymphoma/leukemia must meet the following criteria:
• 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.
• Note: Subjects must have been adequately treated and failed or relapsed after guideline-recommended first-line therapy (including anti-CD20 monoclonal antibody combination therapy or BTK inhibitors).
• \) B-cell lymphoma/leukemia patients with bone marrow relapse must meet the following criteria:
• Definition of relapse: Hematological relapse: re-emergence of B-lymphoma cells ( 5%) in peripheral blood or bone marrow in patients who achieved CR, or appearance of extramedullary disease; OR bone marrow or peripheral blood molecular relapse: MRD positivity reappears after HCR and MRD negativity, with an increase of 1 log in MRD levels between two positive samples.
• Definition of refractory: Failure to achieve CR after at least two cycles of standard chemotherapy; or failure to achieve CR after at least one cycle of treatment following late relapse ( 12 months) after CR; or relapse after HSCT; or patients undergoing salvage therapy after HSCT failing to achieve remission after the last treatment; or Philadelphia chromosome-positive patients who failed to achieve CR or relapsed after at least two types of TKI treatment, or are intolerant/contraindicated to TKI treatment.
• \) Patients unsuitable for stem cell transplantation, or with documented refusal of other existing treatments, or for whom no standard treatment plan exists, may also be included.
• CD19 expression: CD19 positivity detected by IHC or FACS in tumor specimens, bone marrow, or peripheral blood during screening.
• Measurable disease: B-cell lymphoma subjects must have measurable lesions per Lugano 2014 (LDi \> 1.5 cm for nodal, LDi \> 1.0 cm for extranodal); B-lymphoma/leukemia subjects must have B-lymphoma cell proportion 5% at screening.
• ECOG performance status: 0-2.
• Life expectancy: 12 weeks.

You may not qualify if:

• Prior antitumor therapy (except drugs proven to enhance or not affect CAR-T efficacy after elution):
• 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.
• Immunosuppressive therapy within 4 weeks before administration or requirement for long-term use.
• Radiotherapy within 4 weeks before administration.
• Bendamustine within 6 months before administration.
• Previous gene therapy products, including CAR-T therapy (except patients with no CAR-T in vivo, normal T-cell count/function, and CD19+ tumor).
• Previous anti-CD19/anti-CD3 or any other anti-CD19 therapy (except patients with normal T-cell count/function and CD19+ tumor).
• Other interventional clinical trial drugs or antitumor therapies within 4 weeks or 5 half-lives before administration (whichever is shorter).
• Other malignancies: Malignancies within 2 years before screening, excluding adequately treated cervical carcinoma in situ, skin cancers, or radically treated localized prostate, breast (DCIS), or papillary thyroid cancers.
• Organ transplant: History of solid organ transplantation.
• Immunomodulators: Use within 2 weeks before administration or potential use during the study (e.g., thalidomide, lenalidomide, pomalidomide).
• Corticosteroids: Requirement for long-term therapeutic doses (Prednisone \> 15 mg/day or equivalent), except physiological replacement or topical/inhaled use.

Sponsors & Collaborators

• Ruijin Hospital: lead

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Li Wang

CONTACT

+86 15214370575; wl_wangdong@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Shanghai Institute of Hematology

Study Record Dates

• First Submitted: April 19, 2026
• First Posted: May 13, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): July 20, 2026
• Study Completion (Estimated): April 20, 2029
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share