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

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Brief Title

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

Official Title

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

Brief 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.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Estimate the maximum tolerated dose (MTD) and dose limiting toxicities (DLT), and describe the full toxicity profile of the two CAR T cell products

Secondary Outcome

 Number of Arm A and Arm B subjects with persistence of CAR T cells in the peripheral blood at each visit time point

Condition

Pediatric Solid Tumor

Intervention

second generation 4-1BBζ EGFR806-EGFRt

Study Arms / Comparison Groups

 EGFR 806CAR(2G) -EGFRt
Description:  Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

36

Start Date

June 18, 2019

Completion Date

June 2038

Primary Completion Date

June 2023

Eligibility Criteria

        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
      

Gender

All

Ages

1 Year - 30 Years

Accepts Healthy Volunteers

No

Contacts

Katie Albert, MD, 206-987-2106, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03618381

Organization ID

STRIvE-01


Responsible Party

Principal Investigator

Study Sponsor

Seattle Children's Hospital


Study Sponsor

Katie Albert, MD, Study Chair, Seattle Children's Hospital


Verification Date

April 2021