Phase 2 N=18 Treatment

CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII

Malignant Glioma · Glioblastoma · Brain Cancer · Gliosarcoma

Bottom Line

View on ClinicalTrials.gov: NCT01454596 ↗

Enrolled (actual)

Serious AEs

11.1%

Results posted

Aug 2019

Primary outcome: Primary: Number of Treatment Related Adverse Events — 0; 0; 0; 0 adverse events

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Epidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL (Biological); Aldesleukin (Drug); Fludarabine (Drug); Cyclophosphamide (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Nov 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Treatment Related Adverse Events	0; 0; 0; 0; 0; 0	—
PRIMARY Progression Free Survival	1.1; 1.1; 1.3; 1.9; 2.0; 1.5	—
SECONDARY Number of Patients With an Objective Response	0; 0; 0; 0; 0; 0	—
SECONDARY Circulating Chimeric Antigen Receptor (CAR+) Cells in Peripheral Blood at 1 Month Post Treatment	23; 70; 36; 67; 7; 43	—
SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	1; 1; 1; 1; 1; 1	—

Summary

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with gliomas that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient's white blood cells with a retrovirus that has the gene for epidermal growth factor receptor (EGFR) vIII incorporated in the retrovirus. Objective: The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-EGFRvIII cells) are a safe and effective treatment for advanced gliomas. Eligibility: - Adults age 18-70 with malignant glioma expressing the EGFRvIII molecule. Design: Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-EGFRvIII cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-EGFRvIII cells, and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans every month for the first year, and then every 1-2 months as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Eligibility Criteria

-INCLUSION CRITERIA:

Patients with histologically proven glioblastomas or gliosarcomas that express epidermal growth factor receptor(EGFRv)III as assessed by immunohistochemistry (IHC) or polymerase chain reaction (PCR) confirmed by the National Cancer Institute (NCI) Laboratory of Pathology.
Patients must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered no evidence of disease (NED)). This includes recurrent glioblastoma (GBM) after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy.
Patients must either not be receiving steroids, or be on a stable dose of steroids for at least five days prior to registration.
Age greater than or equal to 18 years and less than or equal to age 70 years.
Ability of subject to understand and the willingness to sign a written informed consent document.
Willing to sign a durable power of attorney.
Karnofsky Performance Status (KPS) greater than or equal to 60
Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
Serology
Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by Reverse transcription polymerase chain reaction (RT-PCR) and be Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) negative.
Hematology
White blood cell (WBC) greater than or equal to 3000/mm(3)
Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3) without the support of filgrastim
Platelet count greater than or equal to 100,000/mm(3)
Hemoglobin greater than or equal to 8.0 g/dl. Subjects may be transfused to reach this cut-off.
Chemistry
Serum Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) less than or equal to 2.5 x ULN
Serum creatinine less than or equal to 1.6 mg/dl
Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome, who must have a total bilirubin equal to or less than 3.0 mg/dl.
Patients must be at least 4 weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, 2 weeks from vincristine and 4 weeks from last bevacizumab administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents. All toxicities from prior therapies should be resolved to Common Terminology Criteria in Adverse Events (CTCAE) less than or equal to grade 1 (except for toxicities such as alopecia, or vitiligo).
Subject's must be co-enrolled on protocol 03-C-0277

EXCLUSION CRITERIA

A prior history of gliadel implantation in the past six months..
Women of child-bearing potential who are pregnant or breast feeding because of the potentially dangerous effects of the treatment on the fetus or infant.
Active systemic infections, requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
Concurrent opportunistic infections (The experimental treatment being eval

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Data sourced from ClinicalTrials.gov (NCT01454596). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.