B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

STATUS

Recruiting
End date

Dec 5, 2040
participants needed

68
sponsor

Seattle Children's Hospital

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Updated on 19 February 2024

See if I qualify

suicide

corticosteroids

solid tumour

solid tumor

stem cell transplantation

trastuzumab

cetuximab

steroid therapy

corticosteroid therapy

stem cell infusion

biological therapy

recurrent disease

apheresis

antibody therapy

iobenguane

stem cell transplant

biotherapy

systemic corticosteroid therapy

mibg

tumors in children

biologic therapy

cytokine release syndrome

metaiodobenzylguanidine

pediatric

neuroblastoma

i131 mibg therapy

Summary

Show definitions

This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS solid tumors to evaluate the safety, feasibility, and efficacy of administering T cell products derived from the research participant's blood that have been genetically modified to express a B7H3-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express B7H3. On Arm A of the study, research participants will receive B7H3-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at B7H3 and CD19, a marker on the surface of B lymphocytes, following the hypothesis that CD19+ B cells serving in their normal role as antigen presenting cells to T cells will promote the expansion and persistence of the CAR T cells. Arm A CAR T cells include the protein EGFRt and Arm B CAR T cells include the protein HER2tG. These proteins can be used to both track and destroy the CAR T cells in case of undue toxicity. The primary objectives of the study will be to determine the feasibility of manufacturing the cell products, the safety of the T cell product infusion, to determine the maximum tolerated dose of the CAR T cells products, to describe the full toxicity profile of each product, and determine the persistence of the modified cell in the participant's body on each arm. Participants will receive a single dose of T cells comprised of two different subtypes of T cells (CD4 and CD8 T cells) felt to benefit one another once administered to the research participants for improved potential therapeutic effect. The secondary objectives of this protocol are to study the number of modified cells in the patients and the duration they continue to be at detectable levels. The investigators will also quantitate anti-tumor efficacy on each arm. Participants who experience significant and potentially life-threatening toxicities (other than clinically manageable toxicities related to T cells working, called cytokine release syndrome) will receive infusions of cetuximab (an antibody commercially available that targets EGFRt) or trastuzumab (an antibody commercially available that targets HER2tG) to assess the ability of the EGFRt on the T cells to be an effective suicide mechanism for the elimination of the transferred T cell products.

Details

Condition	Connective and Soft Tissue Neoplasm, Solid Tumors, Malignant neoplasm of kidney, kidney cancer, Rhabdoid Tumor, Hepatoblastoma, Hepatoblastoma, Carcinoma, vulvar dysplasia and carcinoma, Ewing's sarcoma, Osteosarcoma, Osteosarcoma, Nerve Sheath Tumors, melanoma, Metastatic Melanoma, melanoma, Hereditary Neoplastic Syndrome, hereditary cancer syndromes, skin cancer, skin cancer, Desmoplastic Small Round Cell Tumor, synovial sarcoma, Nephroblastoma, Rhabdomyosarcoma, Rhabdomyosarcoma, Clear cell sarcoma, Retinoblastoma, Retinoblastoma, Neuroblastoma, Neuroblastoma, Sarcoma, Sarcoma, Germ cell tumor, Metastatic Melanoma, Pediatric Solid Tumor, Solid Tumors, vulvar dysplasia and carcinoma, kidney cancer, hereditary cancer syndromes
Age	26years or below
Treatment	second generation 4-1BBζ B7H3-EGFRt-DHFR, second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
Clinical Study Identifier	NCT04483778
Sponsor	Seattle Children's Hospital
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Participants age 26 years at the time of consent for study participation; the first 2 participants enrolled and treated with CAR T cells in both Arms A and B will be 15 years. and 26 years at time of consent for study participation
	Histologically diagnosed malignant, non-primary CNS solid tumor
	Evidence of refractory or recurrent disease
	Lansky or Karnofsky score 50
	Life expectancy 8 weeks
	Recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy and radiotherapy
	If no apheresis product or usable T cell product is available, all chemotherapy has been discontinued 7 days prior to enrollment
	If no apheresis or usable T cell product is available, all biologic therapy has been discontinued 7 days prior to enrollment
	If no apheresis product or T cell product is available, all systemic corticosteroid therapy has been discontinued 7 days prior to enrollment
	If no apheresis product or usable T cell product is available, at least 3 half-lives or 30 days (whichever is shorter) from time of last dose of anti-tumor directed antibody therapy at time of enrollment
	If no apheresis product or usable T cell product is available, at least 6 weeks post last dose of myeloablative therapy and autologous and/or allogeneic stem cell transplant, or non-myeloablative therapy and allogeneic stem cell transplant (all timed from stem cell infusion). Participants who receive autologous stem cell infusion following non-myeloablative therapy are eligible once all other eligibility requirements are met
	Participants with neuroblastoma must be at least 12 weeks from I131 MIBG therapy
	Adequate organ function
	Adequate laboratory values
	Participant is able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary
	Participants of childbearing potential must agree to use highly effective contraception
Exclusion Criteria
	Presence of active malignancy other than primary malignant solid tumor diagnosis
	Current relevant CNS pathology
	Receiving external beam radiation therapy
	Presence of active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
	Participant is pregnant or breastfeeding
	Participant has presence of active severe infection
	Participant has presence of any condition that, in the option of an investigator, would prohibit the participant from undergoing treatment under this protocol
	Participant has primary immunodeficiency syndrome
	Unwilling or unable to provide consent/assent for participation in the study and 15 year follow up period

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Navin Pinto, MD

Primary Contact

Seattle Children's Hospital

Seattle WA United States

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stem cell transplantation

trastuzumab

cetuximab

steroid therapy

corticosteroid therapy

systemic corticosteroid therapy

mibg

tumors in children

biologic therapy

cytokine release syndrome

metaiodobenzylguanidine

pediatric

neuroblastoma

i131 mibg therapy

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B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults