Autologous B7-H3 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2-30
SponsorStanford University
About this trial
The purpose of this study is to test the manufacturing feasibility and safety of intravenous (IV) administration of B7-H3CART in children and young adult subjects with relapsed and/or refractory solid tumors expressing B7-H3 target using a standard 3+3 dose escalation design.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed malignant solid tumor (including neuroblastoma, soft tissue sarcoma, osteosarcoma, Ewing Sarcoma, and Wilms tumor) with evidence of incurable disease and tumor recurrence/progression after all available curative standard therapies.
Subjects with neuroblastoma must have received or be intolerant to anti-GD2 antibody therapy.
Subjects with Wilm's tumor must have received or be intolerant to ifosfamide or cyclophosphamide plus etoposide therapy or alternative salvage regimen.
Subjects with embryonal rhabdomyosarcoma must have received or be intolerant to Adriamycin-based therapy.
Disqualifiers
Receiving any other current investigational agents.
History of other malignancy, except non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless disease free for at least 3 years.
Presence of untreated brain metastases will be excluded. Subjects with previous CNS tumor involvement that has been treated and is stable for at least 3 months following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted.
Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
Trial design
Design model
Sequential
Treatments tested in this trial
B7-H3CART Dose (Intravenous)
DrugSubjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level -1 (DL-1) 0.3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 1 (DL1) 1 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 3 (DL3) 9 x 106 transduced T cells/kg
Treatment groups
41 Participants
are divided into 1 treatment groupGroup A: LymphodepletionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Feasibility of manufacturing autologous T cells
Feasibility of manufacturing autologous T cells transduced with Ef1a-CAR276 lentiviral vector expressing B7-H3 Chimeric Antigen Receptor (B7-H3-CART), using the Miltenyi CliniMACS Prodigy® system with dasatinib and protamine sulfate.
Time frame
2 years2
Safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART
Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART in children and young adults with relapsed and refractory solid tumors (i.e. soft tissue sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma) using the proposed dose escalation schedule.
Time frame
2 yearsSecondary outcomes
1
Clinical response in children and young adults
Assess clinical response in children and young adults with relapsed and refractory solid tumors treated with IV B7-H3CART.
Time frame
2 years2
Safety of B7-H3CART at the MTD/RP2D
Assess the safety of B7-H3CART at the MTD/RP2D in children and young adults with relapsed and refractory solid tumors treated with IV B7-H3CART.
Time frame
2 yearsSponsors and contacts
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Source ClinicalTrials.gov