EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Brain Cancer, Neurology |
| Therapuetic Areas: | Neurology, Oncology |
| Healthy: | No |
| Age Range: | 1 - 26 |
| Updated: | 4/6/2019 |
| Start Date: | October 2019 |
| End Date: | October 2036 |
| Contact: | Katie Albert, MD |
| Email: | immunotherapy@seattlechildrens.org |
| Phone: | 206-987-2106 |
Phase I Study of EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
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.
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.
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
We found this trial at
1
site
4800 Sand Point Way NE
Seattle, Washington 98105
Seattle, Washington 98105
(206) 987-2000
Principal Investigator: Katie Albert, MD
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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