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

  • STATUS
    Recruiting
  • End date
    Dec 27, 2040
  • participants needed
    68
  • sponsor
    Seattle Children's Hospital
Updated on 27 April 2021
stem cell transplantation
metastatic disease
biologic agent
cytokines
stem cell infusion
biological factors
chemotherapy regimen
cetuximab
trastuzumab
apheresis
cancer chemotherapy
recurrent disease
biological therapy
solid tumour
solid tumor
antibody therapy
iobenguane
cellular therapy
cytokine release syndrome
tumors in children
biologic therapy
mibg

Summary

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, Malignant neoplasm of kidney, Rhabdoid Tumor, Hepatoblastoma, Carcinoma, Ewing's sarcoma, Osteosarcoma, Nerve Sheath Tumors, melanoma, Hereditary Neoplastic Syndrome, skin cancer, Desmoplastic Small Round Cell Tumor, synovial sarcoma, Nephroblastoma, Rhabdomyosarcoma, Clear cell sarcoma, Retinoblastoma, Neuroblastoma, Sarcoma, Germ cell tumor, Metastatic Melanoma, Vulvar Dysplasia and Carcinoma, All Solid Tumors, Solid Tumors, Solid Tumor, Pediatric Solid Tumor, Advanced Malignancies, Sarcoma (Pediatric), Kidney Cancer, Malignant Melanoma, Wilms' Tumor, Germ Cell Tumors, Hereditary Cancer Syndromes, Renal Cancer, Soft Tissue Sarcoma, mpnst, bone sarcoma, sarcomas, soft tissue sarcomas, carcinomas, neuroblastomas
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 IdentifierNCT04483778
SponsorSeattle Children's Hospital
Last Modified on27 April 2021

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 (physiologic replacement dosing is allowed)
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 (including checkpoint inhibitor) 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
If no apheresis product or usable T cell product is available, participants who have received genetically modified cell therapy must be at least 30 days from most recent cell infusion prior to enrollment
Adequate organ function
If no apheresis product or usable T cell product is available, participants with neuroblastoma must be at least 12 weeks from I131 MIBG therapy
Adequate laboratory values
Participant is able to tolerate apheresis (including placement of temporary apheresis catheter, if necessary), or already has an apheresis product available for use in manufacturing
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
Presence of active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
Receiving external beam radiation therapy at time of 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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