Clinical trial NCT06221553: Safety and Efficacy of Loco-regional B7H3 IL-7Ra CAR T Cell in DIPG
Official title: Safety and Efficacy of Intraventricular Infusion of B7H3 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell in Diffuse Intrinsic Pontine Glioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: DIPG Brain Tumor
Diffuse Intrinsic Pontine Glioma
Keywords: CAR T cell
DIPG
B7H3
IL-7 receptor alpha
Chimeric antigen receptor T cell
Adoptive cellular therapy
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
Collaborators: name: King Chulalongkorn Memorial Hospital
First posted: 2024-01-24
Enrollment: 9
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 3+3 dose escalation study
Primary purpose: TREATMENT

Brief summary: A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cell with IL-7Ra signal targeting B7H3 in children with diffuse intrinsic pontine glioma (DIPG) patients after complete standard treatments.

Detailed description: The brain tumor known as Diffuse Intrinsic Pontine Glioma is commonly found in children aged between 5 to 10 years. This type of tumor is aggressive and infiltrates the structures of the brain stem. Treatment options are limited due to the location of the tumor, making it impossible to surgically remove the mass like other brain cancers. The standard treatment for this type of tumor is radiation therapy, as this type of cancer does not respond to chemotherapy or currently available targeted drugs. However, radiation therapy has been found to be ineffective and does not improve survival rates.

Currently, there is development in cancer treatment using immunotherapy, where the patient's immune cells are genetically modified to target the cancer, also known as CAR T cells, for the treatment of recurrent or refractory cancers in solid tumors and brain cancers. The research project aims to study the efficacy and safety of treating patients with pontine glioma using T cells that are antigen-specific and have signals from the interleukin-7 receptor alpha and are specific to the B7H3 antigen on the tumor surface. This research is the first of its kind in Thai patients. The research project expects that this treatment will be highly safe and effective in controlling diffuse pontine glioma.

Eligibility criteria: Inclusion Criteria:

1. Participants must have diffuse intrinsic pontine glioma at any timepoint following completion of standard radiotherapy
2. Age 1-18 years
3. Sex: Male or female
4. CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy
5. Performance status: Lansky or Karnofsky score \&gt;= 60
6. Life expectancy \&gt;= 8 weeks
7. Normal organ function:

   7.1 AST (SGOT) \&lt; 5 times the upper limit of normal (ULN) 7.2 ALT (SGPT) \&lt; 5 times the upper limit of normal (ULN) 7.3 Total bilirubin \&lt; 3 times the upper limit of normal (ULN) 7.4 Creatinine \&lt; 5 times the upper limit of normal (ULN) 7.5 SpO2 room air \&gt;=90%
8. Prior therapy wash-out before planned leukapheresis 8.1 \&gt;= 7 days post last chemotherapy/biologic therapy administration 8.2 3 half-lives or 30 days, whichever is shorter after the last dose of antitumor antibody therapy 8.3 At least 30 days from most recent cellular infusion 8.4 All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with a maximum dexamethasone dose of 2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed
9. Participants and/or legal guardians must have the ability to understand and willingness to sign a written informed consent and/or assent document

Exclusion Criteria:

1. Presence of \&gt;= grade 3 cardiac dysfunction or symptomatic arrythmia requiring intervention
2. Presence of primary immunodeficiency or bone marrow failure syndrome
3. Presence of clinical and/or radiographic evidence of impending herniation of CNS
4. Presence of \&gt; Grade 3 dysphagia
5. History of active malignancy other than nonmelanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast).
6. Presence of uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Pregnant or breastfeeding women were excluded from this study because CAR-T-cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment in this study and for four months after receiving CAR-T-cell infusion.
8. Serologic status reflecting active HIV, hepatitis B or C infection. Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen or hepatitis C antibody must have negative PCR prior to enrollment.

Primary outcomes:
measure: Safety of B7H3-IL7Ra CAR T cells infusion in diffuse intrinsic pontine glioma (DIPE) patients.
timeFrame: Up to 28 days after B7H3-IL7Ra CAR-T cell infusion
Secondary outcomes:
measure: The overall response rate of diffuse intrinsic pontine glioma (DIPE)
timeFrame: 3, 6, and 12 months after B7H3-IL7Ra CAR-T cell infusion
Other outcomes:
measure: The persistence and distribution of B7H3-IL7Ra CAR T cells in the CSF and peripheral blood
timeFrame: 14 days, 28 days, 42 days 3 months, 6 months, and 12 months after B7H3-IL7Ra CAR-T cell infusion
measure: Serum cytokine level measurement
timeFrame: 1 day, 14 days, 28 days and 42 days after B7H3-IL7Ra CAR-T cell infusion.
Locations:
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
state: Pathumwan
Study officials:
affiliation: Chulalongkorn University
name: Piti Techavichit, MD
role: PRINCIPAL_INVESTIGATOR
References: