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

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ClinicalTrials.gov Identifier: NCT03618381
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
Julie Park, Seattle Children's Hospital

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 the first arm of the study, research participants will receive EGFR-specific CAR T cells only. On the second arm 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) 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.

Condition or disease Intervention/treatment Phase
Pediatric Solid Tumor Biological: second generation 4-1BBζ EGFR806-EGFRt Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : September 3, 2021
Estimated Study Completion Date : September 3, 2036

Arm Intervention/treatment
Experimental: EGFR 806CAR(2G) -EGFRt
Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt
Biological: second generation 4-1BBζ EGFR806-EGFRt
Autologous CD4 and CD8 T cells lentivirally transduced to express a second generation 4-1BBζ EGFR806-EGFRt

Experimental: EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG
Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG
Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Autologous CD4 and CD8 T cells lentivirally transduced to express a second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG




Primary Outcome Measures :
  1. Establish the safety, defined by adverse events, of EGFR806-specific CAR T cell infusions (Arm A), and of dual transduced EGFR806xCD19 CAR T cell infusions (Arm B) [ Time Frame: 28 Days ]
    Type, frequency, severity, and duration of adverse events will be tabulated and summarized

  2. The number of successfully manufactured EGFR806 and EGFR806xCD19 CAR T cell products will be assessed [ Time Frame: 28 Days ]
    The number of successfully manufactured products will be measured


Secondary Outcome Measures :
  1. Number of Arm A and Arm B subjects with persistence of CAR T cells in the peripheral blood at each visit time point [ Time Frame: 84 Days ]
    Presence of CAR T cells in the peripheral blood will be assessed

  2. Number of Arm A and Arm B subjects with persistence of CAR T cells in the bone marrow at each visit time point [ Time Frame: 84 days ]
    Presence of CAR T cells in the bone marrow will be assessed


Other Outcome Measures:
  1. To quantitate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations and describe survival characteristics following CAR T cell infusion [ Time Frame: 84 Days ]
    Standard imaging and bone marrow pathology will be used to determine disease response



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 26 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • First 2 subjects enrolled and treated in both Arm A and Arm B: age ≥ 15 and ≤ 26 years
  • Subsequent subjects: age ≥ 1 and ≤ 26 years
  • Histologically diagnosed malignant, non-CNS solid tumor expressing EGFR
  • Evidence of refractory or recurrent disease
  • Able to tolerate apheresis
  • Life expectancy ≥ 8 weeks
  • Lansky or Karnofsky score ≥ 50
  • Recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
  • ≥ 7 days post last chemotherapy/biologic therapy administration
  • ≥ 3 half lives or 30 days, whichever is shorter, post last dose of anti-tumor antibody therapy
  • No prior virotherapy. Prior genetically modified cell therapy is allowed if not detectable at enrollment.
  • ≥ 6 weeks post last dose of myeloablative therapy and allogeneic or autologous stem cell transplant
  • ≥ 6 weeks post non-myeloablative therapy and allogeneic stem cell transplant
  • Subjects who receive autologous stem cell infusion following non-myeloablative therapy are eligible once all other eligibility requirements are met
  • ≥ 7 days post last corticosteroid therapy
  • Must not be receiving external beam radiation therapy at the time of study enrollment; 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 any anti-cancer agents or chemotherapy
  • Pregnant or breastfeeding
  • Unwilling or unable 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03618381


Contacts
Contact: Katie Albert, MD 206-987-2106 immunotherapy@seattlechildrens.org

Locations
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Katie Albert, MD         
Principal Investigator: Katie Albert, MD         
Sponsors and Collaborators
Seattle Children's Hospital
Investigators
Study Chair: Katie Albert, MD Seattle Children's Hospital

Responsible Party: Julie Park, Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT03618381     History of Changes
Other Study ID Numbers: STRIvE-01
First Posted: August 7, 2018    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Julie Park, Seattle Children's Hospital:
CAR T cell
Pediatric
Young Adults
Non-CNS solid tumor