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

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Brief Title

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

Official Title

Phase I Study of B7H3 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 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.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Assess the safety and tolerability of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express B7H3-specific CAR (Arm A)

Secondary Outcome

 Determine the duration of in vivo persistence of adoptively transferred T cells in the peripheral blood and compare engraftment between T cell products

Condition

Pediatric Solid Tumor

Intervention

second generation 4-1BBζ B7H3-EGFRt-DHFR

Study Arms / Comparison Groups

 SCRI-CARB7H3(s)
Description:  Autologous CD4+ and CD8+ T-cells genetically modified to express an B7H3-specific CAR

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

68

Start Date

July 13, 2020

Completion Date

December 2040

Primary Completion Date

December 2025

Eligibility Criteria

        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

          -  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 organ function

          -  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

          -  Receiving external beam radiation therapy at time of enrollment

          -  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
      

Gender

All

Ages

N/A - 26 Years

Accepts Healthy Volunteers

No

Contacts

Navin Pinto, MD, 206-987-2106, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04483778

Organization ID

STRIvE-02


Responsible Party

Principal Investigator

Study Sponsor

Seattle Children's Hospital


Study Sponsor

Navin Pinto, MD, Principal Investigator, Seattle Children's Hospital


Verification Date

April 2021