Back to resultsClinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection
Primary Purpose
Brain Gliomas
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Allogenic B7H3 CAR-γδT cell
Sponsored by
About this trial
This is an interventional treatment trial for Brain Gliomas focused on measuring B7H3, CAR-γδT, GBM
Eligibility Criteria
Inclusion Criteria: 1)Age 18-70 years old (both ends included), both male and female; 2)At least one evaluable lesion with previous biopsy or pathohistologic confirmation of high-grade glioma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment; 3) Surgically resected pathological tissue capable of being used for immunohistochemical detection of target proteins and positive for B7H3 expression; 4) KPS ≥ 60 points; 5)Expected survival > 3 months; 6)Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection for the first time):White blood cell count (WBC) ≥ 3 x 109/L;Lymphocyte count (LY) ≥ 0.8 x 109/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×109/L;Albumin transaminase (ALT) & albumin transaminase (AST) <1.5×ULN;Serum creatinine (Cr) <1.5 x ULN;Total bilirubin < 1.5 x ULN;PT & PTT ≤ 1.25 x ULN. 7)No obvious hereditary diseases; 8)Normal cardiac function with cardiac ejection index >55%; 9)No bleeding and coagulation disorders; 10)Women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion; 11) Sign the informed consent form. Exclusion Criteria: 1)Pregnant and lactating women; 2)Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4 or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory failure with involvement of other organs;Brain: central nervous system abnormalities or impaired consciousness; 3)patients with combined second tumors; 4)patients with active hepatitis B or C virus, HIV infection, or other untreated active infection; 5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis; 6)Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances; 7) have a chronic disease requiring immunologic or hormonal therapy; 8) have an allergy to immunotherapy and related cells; 9) 10)Patients with a history of organ transplantation or who are awaiting organ transplantation; 10)Participation in other clinical trials within the previous 30 days; 11)Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.
Sites / Locations
- Dushu Lake Hospital Affiliated to Soochow UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARM
Arm Description
Patients with refractory or relapsed B7H3 positive GBM
Outcomes
Primary Outcome Measures
Phase 1: Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
DLT was defined as B7H3 CAR-γδT cells-related events with onset within first 28 days following infusion:
The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting > 2 weeks; Any B7H3 CAR-γδT cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Phase 1:Maximum tolerated dose (MTD)
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Phase 1: Recommended phase 2 dose (RP2D)
The recommended dose for phase 2 was determined through phase 1 study.
Phase 2: Best objective Response Rate
The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RANO assessment criterion.
Secondary Outcome Measures
Phase 2: Overall Survival (OS)
OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RANO assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Pharmacokinetics: Number and copy number of B7H3 CAR-γδT cells (phase 1 and phase 2)
Number and copy number of B7H3 CAR-γδT cells were assessed by number in cerebrospinal fluid(CSF). CSF samples were collected before and after cell infusion to detect the number and copy number of B7H3 CAR-γδT cells, and to evaluate the pharmacokinetics of B7H3 CAR-γδT.
Pharmacodynamics: Peak level of cytokines in CSF (phase 1 and phase 2)
The cytokines mainly include interleukin-1 (IL-1 ), IL-6, IL-8, IL-10, interferon-γ (IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.
Full Information
NCT ID
NCT06018363
First Posted
August 25, 2023
Last Updated
August 25, 2023
Sponsor
Dushu Lake Hospital Affiliated to Soochow University
1. Study Identification
Unique Protocol Identification Number
NCT06018363
Brief Title
Clinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection
Official Title
Allogenic B7H3-targeting CAR-γδT Cell Therapy in r/r GBM
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dushu Lake Hospital Affiliated to Soochow University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a study on the clinical application of chimeric antigen receptor modified γδ T cells (CAR-γδ T cells) in relapsed and refractory B7H3 Positive malignant brain glioma.The main purpose of this study was to evaluate the safety and feasibility of CAR-γδ T cell infusion in patients with relapsed and refractory B7H3 Positive malignant brain glioma.
Detailed Description
γδT cells are known as "a great candidate for car-t cells". Although they only account for 2% - 5% of all T cells in our body, they are a natural killer.
Treatment on this study includes six B7H3 CAR-γδ Tcell infusions over an 12 week period. B7H3 CAR-γδ T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety, feasibility and maximum tolerated dose (MTD) of B7H3 CAR-γδ T cell using a 3+3 study design and an 4 week evaluation period. The total study duration will be 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Gliomas
Keywords
B7H3, CAR-γδT, GBM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARM
Arm Type
Experimental
Arm Description
Patients with refractory or relapsed B7H3 positive GBM
Intervention Type
Biological
Intervention Name(s)
Allogenic B7H3 CAR-γδT cell
Intervention Description
Phase 1 dose escalation (3+3) : dose 1 (1 × 10^7 cells) , dose 2 (3 × 10^7 cells), dose 3 (1× 10^8 cells); Phase 2 : dose of RP2D.
Primary Outcome Measure Information:
Title
Phase 1: Incidence of Adverse Events (AEs)
Description
AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Time Frame
12 months
Title
Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
Description
DLT was defined as B7H3 CAR-γδT cells-related events with onset within first 28 days following infusion:
The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting > 2 weeks; Any B7H3 CAR-γδT cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Time Frame
First infusion date of B7H3 CAR-γδT cells up to 28 days
Title
Phase 1:Maximum tolerated dose (MTD)
Description
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Time Frame
First infusion date of B7H3 CAR-γδT cells up to 28 days
Title
Phase 1: Recommended phase 2 dose (RP2D)
Description
The recommended dose for phase 2 was determined through phase 1 study.
Time Frame
First infusion date of B7H3 CAR-γδT cells up to 28 days
Title
Phase 2: Best objective Response Rate
Description
The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the RANO assessment criterion.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Phase 2: Overall Survival (OS)
Description
OS is defined as the time from B7H3 CAR-γδT cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Time Frame
12 months
Title
Phase 2: Progression Free Survival (PFS)
Description
PFS is defined as the time from the B7H3 CAR-γδT cells infusion date to the date of disease progression assessed by investigators and based on the RANO assessment criterion, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Time Frame
12 months
Title
Pharmacokinetics: Number and copy number of B7H3 CAR-γδT cells (phase 1 and phase 2)
Description
Number and copy number of B7H3 CAR-γδT cells were assessed by number in cerebrospinal fluid(CSF). CSF samples were collected before and after cell infusion to detect the number and copy number of B7H3 CAR-γδT cells, and to evaluate the pharmacokinetics of B7H3 CAR-γδT.
Time Frame
First infusion date of B7H3 CAR-γδT cells up to 28 days
Title
Pharmacodynamics: Peak level of cytokines in CSF (phase 1 and phase 2)
Description
The cytokines mainly include interleukin-1 (IL-1 ), IL-6, IL-8, IL-10, interferon-γ (IFN-γ). Peak was defined as the maximum post-baseline level of the cytokine.
Time Frame
First infusion date of B7H3 CAR-γδT cells up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1)Age 18-70 years old (both ends included), both male and female;
2)At least one evaluable lesion with previous biopsy or pathohistologic confirmation of high-grade glioma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment;
3) Surgically resected pathological tissue capable of being used for immunohistochemical detection of target proteins and positive for B7H3 expression;
4) KPS ≥ 60 points;
5)Expected survival > 3 months;
6)Substantially normal bone marrow reserve function and normal liver and renal function (laboratory tests need to be fulfilled before receiving QH104 Cell Injection for the first time):White blood cell count (WBC) ≥ 3 x 109/L;Lymphocyte count (LY) ≥ 0.8 x 109/L;Hemoglobin (Hb) ≥ 90g/L;Platelet (PLT) ≥80×109/L;Albumin transaminase (ALT) & albumin transaminase (AST) <1.5×ULN;Serum creatinine (Cr) <1.5 x ULN;Total bilirubin < 1.5 x ULN;PT & PTT ≤ 1.25 x ULN.
7)No obvious hereditary diseases;
8)Normal cardiac function with cardiac ejection index >55%;
9)No bleeding and coagulation disorders;
10)Women of childbearing age (15-49 years old) must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception during the clinical trial and for 3 months after the last cell infusion;
11) Sign the informed consent form.
Exclusion Criteria:
1)Pregnant and lactating women;
2)Those with organ failure:Heart: Class III and IV;Liver: up to grade C of the Child-Turcotte Liver -Function Classification;Kidney: chronic kidney disease stage 4 or above; renal insufficiency stage III or above;Lungs: symptoms of severe respiratory failure with involvement of other organs;Brain: central nervous system abnormalities or impaired consciousness;
3)patients with combined second tumors;
4)patients with active hepatitis B or C virus, HIV infection, or other untreated active infection;
5)any severe, uncontrolled systemic autoimmune disease or any unstable systemic disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis;
6)Current systemic use of steroid cell (except for recent or current use of inhaled steroids) substances;
7) have a chronic disease requiring immunologic or hormonal therapy;
8) have an allergy to immunotherapy and related cells;
9) 10)Patients with a history of organ transplantation or who are awaiting organ transplantation;
10)Participation in other clinical trials within the previous 30 days;
11)Those who are not suitable for clinical trials for other reasons in the opinion of the investigator.
Facility Information:
Facility Name
Dushu Lake Hospital Affiliated to Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215125
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yulun Huang
Phone
+86 130 1388 9432
Email
huangyulun@suda.edu.cn
First Name & Middle Initial & Last Name & Degree
Xuetao Li
Phone
+86 151 9563 7789
Email
lixuetao0405@126.com
First Name & Middle Initial & Last Name & Degree
Yulun Huang
First Name & Middle Initial & Last Name & Degree
Xuetao Li
12. IPD Sharing Statement
Learn more about this trial
Clinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection
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