EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

  • STATUS
    Recruiting
  • End date
    Jun 30, 2038
  • participants needed
    36
  • sponsor
    Seattle Children's Hospital
Updated on 30 April 2021
stem cell transplantation
metastatic disease
biologic agent
cytokines
stem cell infusion
biological factors
EGFR
chemotherapy regimen
cetuximab
trastuzumab
apheresis
cancer chemotherapy
recurrent disease
biological therapy
solid tumour
solid tumor
antibody therapy
iobenguane
cellular therapy
cytokine release syndrome
viral therapy
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 EGFR-specific receptor (chimeric antigen receptor, or CAR) that will target and kill solid tumors that express EGFR and the selection-suicide marker EGFRt. EGFRt is a protein incorporated into the cell with our EGFR receptor which is used to identify the modified T cells and can be used as a tag that allows for elimination of the modified T cells if needed. On Arm A of the study, research participants will receive EGFR-specific CAR T cells only. On Arm B of the study, research participants will receive CAR T cells directed at EGFR 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. The CD19 receptor harbors a different selection-suicide marker, HERtG. 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 subject's body on each arm. Subjects 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. Subjects 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, Hereditary Neoplastic Syndrome, Desmoplastic Small Round Cell Tumor, synovial sarcoma, Nephroblastoma, Rhabdomyosarcoma, Clear cell sarcoma, Retinoblastoma, Neuroblastoma, Sarcoma, Germ cell tumor, Vulvar Dysplasia and Carcinoma, All Solid Tumors, Solid Tumors, Solid Tumor, Pediatric Solid Tumor, Advanced Malignancies, Sarcoma (Pediatric), Kidney Cancer, 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 EGFR806-EGFRt, second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Clinical Study IdentifierNCT03618381
SponsorSeattle Children's Hospital
Last Modified on30 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

First 2 subjects enrolled and treated in both Arm A and Arm B: age 15 and 30 years
Subsequent subjects: age 1 and 30years
Histologically diagnosed malignant, non-CNS solid tumor expressing EGFR
Evidence of refractory or recurrent disease
Able to tolerate apheresis or has apheresis product available for use in manufacturing
Life expectancy 8 weeks
Lansky or Karnofsky score 50
Recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
If no apheresis product or T cell product is available, 7 days post last chemotherapy/biologic therapy administration
If no apheresis product or T cell product is available, 3 half lives or 30 days, whichever is shorter, post last dose of anti-tumor antibody therapy (including check point inhibitor)
Prior genetically modified cell therapy is allowed if not detectable at enrollment
If no apheresis product or T cell product is available, 6 weeks post last dose of myeloablative therapy and allogeneic or autologous stem cell transplant
Subjects who receive autologous stem cell infusion following non-myeloablative therapy are eligible once all other eligibility requirements are met
If no apheresis product or T cell product is available, 7 days post last systemic corticosteroid therapy (physiologic replacement dosing is allowed)
If no apheresis product or T cell product is available, subjects with neuroblastoma must be 12 weeks from I131 MIBG therapy
Adequate organ function
Adequate laboratory values
Patients 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
Presence of active severe infection
Presence of primary immunodeficiency syndrome
Receiving external beam radiation therapy at time of enrollment
Receiving any anti-cancer agents or chemotherapy
Pregnant or breastfeeding
Unwilling to provide consent/assent for participation in the study and 15 year follow up period
Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
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