Back to results

Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

Primary Purpose

Glioblastoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

B7-H3-targeting CAR-T cells

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, aged 18-75 years (including 18 and 75 years old)；
Patients with relapsed glioblastoma, as confirmed by positron emission tomography (PET) or histologic pathology；
A >= 30% staining extent of B7-H3 in his/her primary/recurrent tumor tissue by the immunochemical method;
Karnofsky scale score>=50
Availability in collecting peripheral blood mononuclear cells (PBMCs) ；
Adequate laboratory values and adequate organ function;
Patients with childbearing/fathering potential must agree to use highly effective contraception；

Exclusion Criteria:

Pregnant or breastfeeding females；
Contraindication to bevacizumab；
Within 5 days before the CAR-T cell infusion, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids ( not including inhaled corticosteroid)；
Comorbid with Other uncontrolled malignancy；
Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection;
Subjects receiving the placement of a carmustine slow-release wafer within 6 months before the enrollment;
Autoimmune diseases;
Receiving long-term immunosuppressive treatment after organ transplantation;
Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;
Not recovered from the toxicities or side effects by previous treatment;
Subjects who have participated the other interventional trial within one month before the enrollment, or have received other CAR-T cell therapies or gene-modified cell therapy before enrollment.
Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures, the medical conditions including, but not limited to cardio-cerebral vascular diseases, renal dysfunction/failure, pulmonary embolism, coagulation disorders, active systemic infection, uncontrolled infection et. al; or patients who are unwilling or unable to comply with the research procedures; these
Subjects with other conditions that would interfere trial participation at the investigator's discretion.

Sites / Locations

Beijing Tiantan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T cell therapy

Arm Description

Dose-escalation phase: A "3+3" dose-escalation design is used to determine MTD & R2PD. Anti-B7-H3 autologous CAR-T cells were given biweekly to patients at the following doses for each cycle, and 4 cycles as one course. Dose1: 3 patients at a dose of 20 million cells for each cycle. Dose 2: 3 patients at a dose of 60 million cells for each cycle. Dose 3: 3 patients at a dose of 150 million cells for each cycle. Dose 4: 3 patients at a dose of 450 million cells for each cycle. Dose 5: 3 patients at a dose of 900 million cells for each cycle. R2PD confirmation phase: Determine the R2PD based on the results from the previous dose-escalation study; Treat another 12 patients with anti-B7-H3 autologous CAR-T cells biweekly at the R2PD to further confirm the safety of R2PD. At each dose phase, if the patients show tolerate and response to the treatment, these patients would receive several courses of treatment at PI's discretion.

Outcomes

Primary Outcome Measures

Incidence of Dose Limiting Toxicity (DLT)

To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion

Safety：Incidence and severity of adverse events

To evaluate the possible adverse events occurred within three months after B7-H3 CAR-T cell infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity

Secondary Outcome Measures

Efficacy：Overall survival rate at 12 months

The proportion of subjects who have survived for more than 12 months since the diagnosis of recurrent glioblastoma

Efficacy：objective remission rate

The proportion of subjects reaching complete remission / partial remission in optimal remission

pharmacokinetics：Cmax

observed maximum plasma concentration (Cmax)

pharmacokinetics：Tmax

time to reach maximum plasma concentration (tmax)

pharmacokinetics：AUC

area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28))

Full Information

NCT ID

NCT05241392

First Posted

January 13, 2022

Last Updated

July 25, 2023

Sponsor

Beijing Tiantan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05241392

Brief Title

Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

Official Title

An Open, Single-arm, Phase 1 Study to Evaluate the Safety/Preliminary Effectiveness and Determine the Maximal Tolerated Dose of B7-H3-targeting CAR-T Cell Therapy in Treating Recurrent Glioblastomas

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 27, 2022 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beijing Tiantan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is an open, single-arm, dose-escalation and multiple-dose study to evaluate the safety, tolerability and preliminary effectiveness of B7-H3-targeting Chimeric Antigen Receptor-T (CAR-T) cell therapy on patients with recurrent glioblastomas. The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

a "3+3" design is used to determine Maximum Tolerated Dose (MTD) and the recommended phase 2 dose (RP2D)

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-T cell therapy

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

B7-H3-targeting CAR-T cells

Intervention Description

Patients will be treated with anti-B7-H3 autologous CAR-T cells that are delivered into the intracranial tumor resection cavity or ventricular system using an Ommaya device.

Primary Outcome Measure Information:

Title

Incidence of Dose Limiting Toxicity (DLT)

Description

To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion

Time Frame

three months post CAR-T cells infusion

Title

Safety：Incidence and severity of adverse events

Description

Time Frame

three months post CAR-T cells infusion

Secondary Outcome Measure Information:

Title

Efficacy：Overall survival rate at 12 months

Description

The proportion of subjects who have survived for more than 12 months since the diagnosis of recurrent glioblastoma

Time Frame

12 months post CAR-T cells infusion

Title

Efficacy：objective remission rate

Description

The proportion of subjects reaching complete remission / partial remission in optimal remission

Time Frame

1, 2, 3, 4, 5, 6 months post CAR-T cells infusion

Title

pharmacokinetics：Cmax

Description

observed maximum plasma concentration (Cmax)

Time Frame

Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections

Title

pharmacokinetics：Tmax

Description

time to reach maximum plasma concentration (tmax)

Time Frame

Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections

Title

pharmacokinetics：AUC

Description

area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28))

Time Frame

Sample taken pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Sample taken pre-injection, and 2,7,13 days post re-injections

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, aged 18-75 years (including 18 and 75 years old)； Patients with relapsed glioblastoma, as confirmed by positron emission tomography (PET) or histologic pathology； A >= 30% staining extent of B7-H3 in his/her primary/recurrent tumor tissue by the immunochemical method; Karnofsky scale score>=50 Availability in collecting peripheral blood mononuclear cells (PBMCs) ； Adequate laboratory values and adequate organ function; Patients with childbearing/fathering potential must agree to use highly effective contraception； Exclusion Criteria: Pregnant or breastfeeding females； Contraindication to bevacizumab； Within 5 days before the CAR-T cell infusion, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids ( not including inhaled corticosteroid)； Comorbid with Other uncontrolled malignancy； Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection; Subjects receiving the placement of a carmustine slow-release wafer within 6 months before the enrollment; Autoimmune diseases; Receiving long-term immunosuppressive treatment after organ transplantation; Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes; Not recovered from the toxicities or side effects by previous treatment; Subjects who have participated the other interventional trial within one month before the enrollment, or have received other CAR-T cell therapies or gene-modified cell therapy before enrollment. Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures, the medical conditions including, but not limited to cardio-cerebral vascular diseases, renal dysfunction/failure, pulmonary embolism, coagulation disorders, active systemic infection, uncontrolled infection et. al; or patients who are unwilling or unable to comply with the research procedures; these Subjects with other conditions that would interfere trial participation at the investigator's discretion.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yang T Zhang, Dr.

Phone

+861059976516

zhangyang8025@yeah.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nan Ji, Dr.

Organizational Affiliation

Beijing Tiantan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Tiantan Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100730

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yang Zhang, Dr.

Phone

010-59976516

zhangyang8025@yeah.net

First Name & Middle Initial & Last Name & Degree

Nan Ji, Dr.

First Name & Middle Initial & Last Name & Degree

Yang Zhang, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35468680

Citation

Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

Results Reference

derived

Learn more about this trial

Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

We'll reach out to this number within 24 hrs