CompletedNCT01454596Updated Aug 21, 2019Results posted

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

A Phase 1/2 interventional study of Epidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL and Aldesleukin in Malignant Glioma, Glioblastoma and Brain Cancer, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-08-21.

Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 18
Allocation: Non-randomized
Ages: 18 Years to 70 Years
Sex: All

Study 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.

Read the detailed description

BACKGROUND:

Patients with recurrent gliomas have very limited treatment options. Epidermal growth factor receptor (EGFR).

(EGFRvIII) is the most common mutant variant of EGFR and is present in 24-67% of patients with glioblastoma.

EGFRvIII expression promotes oncogenesis and is associated with poor prognosis.
EGFRvIII is not expressed in normal tissue and is an attractive target for immunotherapy.
We have constructed a retroviral vector that contains a chimeric antigen receptor (CAR) that recognizes the EGFRvIII tumor antigen, which can be used to mediate genetic transfer of this CAR with high efficiency without the need to perform any selection.

OBJECTIVES:

Primary Objectives

To evaluate the safety of the administration of anti-EGFRvIII CAR engineered peripheral blood lymphocytes in patients receiving the non-myeloablative, lymphodepleting preparative regimen and aldesleukin.
Determine the six month progression free survival of patients receiving anti-EGFRvIII CAR-engineered peripheral blood lymphocytes and aldesleukin following a nonmyeloablative, lymphodepleting preparative regimen.

ELIGIBILITY:

Histologically proven glioblastoma or gliosarcoma expressing EGFRvIII as determined by immunohistochemistry (IHC) or Reverse transcription polymerase chain reaction (RT-PCR)
Failed prior standard treatment with radiotherapy with or without chemotherapy
Karnofsky performance score (KPS) greater than or equal to 60
Cardiac, pulmonary and laboratory parameters within acceptable limits

DESIGN:

The study will be conducted using a Phase I/II design.
Patients will receive a non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumorreactive, CAR gene-transduced peripheral blood mononuclear cells (PBMC), plus intravenous (IV) aldesleukin.
Once the maximum tolerated cell dose (MTD) has been determined, the study will proceed to the phase II portion.
In the phase II portion of the trial, patients will be accrued to two cohorts:
- Patients with recurrent malignant glioma receiving steroids at the time of treatment.
- Patients with recurrent malignant glioma not receiving steroids at the time of treatment.
A total of 107 patients may be enrolled over a period of 7 years.

Conditions studied

Malignant Glioma
Glioblastoma
Brain Cancer
Gliosarcoma

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Keywords

Cell Therapy
Gene Therapy
Immunotherapy
Brain Cancer
Glioma
Glioblastoma

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 449 are open to participants now.

This study's enrollment of 18 is below the median of 36 across 1,617 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
History of coronary revascularization or ischemic symptoms.
Clinically significant hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criteria; patients who with history of prior intratumoral bleeding, however, need to undergo a non-contrast head computed tomography (CT) to exclude acute bleeding.
Other concomitant anti-cancer therapy except corticosteroids.
Any patient known to have left ventricular ejection fraction (LVEF) less than or equal to 45%.
Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history, with cessation within the past two years).
- Symptoms of respiratory dysfunction
Patients who are receiving any other investigational agents.
Documented LVEF less than or equal to 45% tested in patients:
- Age greater than or equal to 65 years
- With clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease and/or chest pain.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 18 participants (actual)

Study arms

Experimental
1/Phase I Arm
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of epidermal growth factor receptor (EGFRv)III Chimeric antigen receptor (CAR) transduced peripheral blood lymphocytes (PBL) + aldesleukin
Biological: Epidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL · Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide
Experimental
2/Phase II Arm
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + maximum tolerated dose (MTD) of anti-EGFRvIII CAR transduced PBL established in Phase I + aldesleukin
Biological: Epidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL · Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide

Interventions

BiologicalEpidermal growth factor receptor(EGFRv)III Chimeric antigen receptor (CAR) transduced PBL
Day 0: Cells will be infused intravenously over 20-30 minutes. Patients will receive two cell doses, 2 hours apart.
DrugAldesleukin
Aldeskeukin 72,000 IU /kg intravenous (IV) or 720,000 IU /kg IV (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).
Also known as: Proleukin
DrugFludarabine
Days -7 to -3: Fludarabine 25 mg /m(2)/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
Also known as: Fludara
DrugCyclophosphamide
Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg /day X 2 days over 1 hr.
Also known as: Cytoxan

What researchers measure

Primary outcomes

Number of Treatment Related Adverse Events
Aggregate of all adverse events ≥Grade 3 that are possibly, probably, and definitely related to treatment. Adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). Per CTCAE, Grade 3 adverse events are severe, Grade 4 is life threatening, and Grade 5 is death.
Time frame: From 4 weeks after cell infusion up to 77 days
Progression Free Survival
Progression was assessed by the Response Assessment in Neuro-Oncology (RANO) criteria and is defined as the circumstance when the magnetic resonance imaging (MRI) scan is ranked -2 (definitely worse) or -3 (development of a new lesion).
Time frame: Time from the date of registration to the date of first observation of progressive disease up to 6 months after end of treatment

Secondary outcomes

Number of Patients With an Objective Response
Objective response was assessed by comparison with baseline dynamic contrast enhanced magnetic resonance imaging with perfusion using Neuro-oncology Working Group proposed guidelines. Complete Response is disappearance of all measurable and non-measurable disease for at least 4 weeks. Partial Response is \>/= 50% decrease in lesions for at least 4 weeks. Stable Disease does not meet the criteria for complete response, partial response or progression and requires stable lesions compared with baseline. Progression is \>/= 25% increase in lesions.
Time frame: 4 weeks after cell infusion and monthly as feasible up to 12 months
Circulating Chimeric Antigen Receptor (CAR+) Cells in Peripheral Blood at 1 Month Post Treatment
CAR and vector presence were quantitated in peripheral blood mononuclear cell (PBMC) samples using established polymerase chain reaction (PCR) techniques
Time frame: 1 month post transplant
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: 51 dys Grp A, Cohort 1; Cohort 2:68 dys; Cohort 3:40 dys; Grp B, Cohort 1:67 dys; Cohort 2:48 dys; Cohort 3:55 dys; Cohort 4: 46 dys; Cohort 5:147 dys; C. Ster/No Ster Grp, Cohort 6:12 mos, 26 dys; Cohort 7:11 mos, 18 dys; Cohort 8:7 dys; Cohort 9:70 dys.

Results

Posted Aug 21, 2019

Participant flow

Participant flow — Overall Study
Milestone	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Started	1	1	1	1	1	1	1	3	3	3	1	1
Completed	1	1	1	1	1	1	1	3	3	2	0	1
Not completed	0	0	0	0	0	0	0	0	0	1	1	0
Withdrew: Death	0	0	0	0	0	0	0	0	0	1	1	0

Outcome measures

PrimaryNumber of Treatment Related Adverse Events

Aggregate of all adverse events ≥Grade 3 that are possibly, probably, and definitely related to treatment. Adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). Per CTCAE, Grade 3 adverse events are severe, Grade 4 is life threatening, and Grade 5 is death.

Time frame:: From 4 weeks after cell infusion up to 77 days
Reported as:: Number · adverse events

Number of Treatment Related Adverse Events
adverse events	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Number of Treatment Related Adverse Events	0	0	0	0	0	0	0	0	0	0	1	1

PrimaryProgression Free Survival

Progression was assessed by the Response Assessment in Neuro-Oncology (RANO) criteria and is defined as the circumstance when the magnetic resonance imaging (MRI) scan is ranked -2 (definitely worse) or -3 (development of a new lesion).

Time frame:: Time from the date of registration to the date of first observation of progressive disease up to 6 months after end of treatment
Reported as:: Median · months

Progression Free Survival
months	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Progression Free Survival	1.1	1.1	1.3	1.9	2.0	1.5	1.2	1.1 (0.9 to 1.3)	2.7 (0.9 to 12.5)	1.1 (1.1 to 1.6)	0	2.0

SecondaryNumber of Patients With an Objective Response

Objective response was assessed by comparison with baseline dynamic contrast enhanced magnetic resonance imaging with perfusion using Neuro-oncology Working Group proposed guidelines. Complete Response is disappearance of all measurable and non-measurable disease for at least 4 weeks. Partial Response is \>/= 50% decrease in lesions for at least 4 weeks. Stable Disease does not meet the criteria for complete response, partial response or progression and requires stable lesions compared with baseline. Progression is \>/= 25% increase in lesions.

Time frame:: 4 weeks after cell infusion and monthly as feasible up to 12 months
Reported as:: Count of participants · Participants

Number of Patients With an Objective Response
Participants	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Number of Patients With an Objective Response	0	0	0	0	0	0	0	0	0	0	0	0

SecondaryCirculating Chimeric Antigen Receptor (CAR+) Cells in Peripheral Blood at 1 Month Post Treatment

CAR and vector presence were quantitated in peripheral blood mononuclear cell (PBMC) samples using established polymerase chain reaction (PCR) techniques

Time frame:: 1 month post transplant
Reported as:: Median · K/µL

Circulating Chimeric Antigen Receptor (CAR+) Cells in Peripheral Blood at 1 Month Post Treatment
K/µL	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Circulating Chimeric Antigen Receptor (CAR+) Cells in Peripheral Blood at 1 Month Post Treatment	23 (23 to 23)	70 (70 to 70)	36 (36 to 36)	67 (67 to 67)	7 (7 to 7)	43 (43 to 43)	28 (28 to 28)	25 (10 to 219)	12 (12 to 12)	67.5 (26 to 109)	NA (NA to NA)	8 (8 to 8)

SecondaryNumber of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Time frame:: 51 dys Grp A, Cohort 1; Cohort 2:68 dys; Cohort 3:40 dys; Grp B, Cohort 1:67 dys; Cohort 2:48 dys; Cohort 3:55 dys; Cohort 4: 46 dys; Cohort 5:147 dys; C. Ster/No Ster Grp, Cohort 6:12 mos, 26 dys; Cohort 7:11 mos, 18 dys; Cohort 8:7 dys; Cohort 9:70 dys.
Reported as:: Count of participants · Participants

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Participants	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
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	1	3	3	3	1	1

Adverse events

Collected over Date treatment consent signed to date off study, approximately 51 days for Group A, Cohort 1; Cohort 2: 68 days; Cohort 3: 40 days; Group B, Cohort 1: 67 days; Cohort 2: 48 days; Cohort 3: 55 days; Cohort 4: 46 days; Cohort 5: 147 days; and Combined Steroids/No Steroids Group, Cohort 6: 12 months and 26 days; Cohort 7: 11 months and 18 days; Cohort 8: 7 days; Cohort 9: 70 days.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group A (Steroids) - Cohort 1: 1x10(7)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group A (Steroids) - Cohort 2: 3x10(7)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group A (Steroids) - Cohort 3: 1x10(8)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group B (No Steroids) - Cohort 1: 1x10(7)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group B (No Steroids) - Cohort 2: 3x10(7)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group B (No Steroids) - Cohort 3: 1x10(8)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group B (No Steroids) - Cohort 4: 3x10(8)	0/1 (0%)	0/1 (0%)	1/1 (100%)
Group B (No Steroids) - Cohort 5: 1x10(9)	0/3 (0%)	0/3 (0%)	3/3 (100%)
Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	0/3 (0%)	0/3 (0%)	3/3 (100%)
Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	0/3 (0%)	0/3 (0%)	3/3 (100%)
Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	1/1 (100%)	1/1 (100%)	1/1 (100%)
Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	0/1 (0%)	1/1 (100%)	1/1 (100%)

Most frequent serious events

Most frequent serious events
Event	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Death not associated with CTCAE term: Multi-organ failureGeneral disorders	0/1	0/1	0/1	0/1	0/1	0/1	0/1	0/3	0/3	0/3	1/1	0/1
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	0/1	0/1	0/1	0/1	0/1	0/1	0/1	0/3	0/3	0/3	0/1	1/1
HypoxiaRespiratory, thoracic and mediastinal disorders	0/1	0/1	0/1	0/1	0/1	0/1	0/1	0/3	0/3	0/3	0/1	1/1

Most frequent other events

Showing 10 of 27

Most frequent other events
Event	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)
Thrombosis/thrombus/embolismVascular disorders	1/1	0/1	0/1	1/1	0/1	0/1	0/1	0/3	0/3	0/3	0/1	0/1
PTT (Partial Thromboplastin Time)Investigations	0/1	0/1	0/1	1/1	0/1	0/1	0/1	0/3	0/3	0/3	0/1	0/1
Potassium, serum-high (hyperkalemia)Metabolism and nutrition disorders	0/1	0/1	0/1	1/1	0/1	0/1	0/1	0/3	0/3	0/3	0/1	0/1
Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders	0/1	0/1	0/1	0/1	1/1	0/1	0/1	0/3	0/3	0/3	0/1	0/1
ConfusionPsychiatric disorders	1/1	0/1	0/1	0/1	1/1	1/1	0/1	1/3	0/3	0/3	0/1	0/1
PlateletsInvestigations	1/1	1/1	1/1	1/1	1/1	1/1	1/1	3/3	3/3	3/3	1/1	1/1
Fatigue (asthenia, lethargy, malaise)General disorders	0/1	0/1	0/1	1/1	0/1	0/1	1/1	1/3	1/3	1/3	0/1	0/1
Leukocytes (total WBC)Investigations	1/1	1/1	1/1	1/1	1/1	1/1	1/1	3/3	3/3	3/3	0/1	0/1
LymphopeniaInvestigations	1/1	1/1	1/1	1/1	1/1	1/1	1/1	3/3	3/3	3/3	1/1	1/1
Neutrophils/granulocytes (ANC/AGC)Investigations	1/1	1/1	1/1	1/1	1/1	1/1	1/1	3/3	3/3	3/3	1/1	1/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	1	1	1	1	1	1	1	3	2	3	1	1	17
>=65 years	0	0	0	0	0	0	0	0	1	0	0	0	1

Age, Continuous
Age, Continuous(years)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
Mean	45.0	43.0	52.0	46.0	57.0	56.0	53.0	55.3 ± 0.6	62.3 ± 3.2	56.0 ± 11.4	47.0	57.0	54.3 ± 7.1

Sex: Female, Male
Sex: Female, Male(Participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
Female	0	0	0	0	0	0	0	1	1	1	0	0	3
Male	1	1	1	1	1	1	1	2	2	2	1	1	15

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
Hispanic or Latino	0	1	0	0	0	0	0	0	0	0	0	0	1
Not Hispanic or Latino	1	0	1	1	1	1	1	3	3	3	1	1	17
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	1	1	0	0	0	0	2
White	1	1	1	1	1	1	0	2	3	3	1	1	16
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
United States	1	1	1	1	1	1	1	3	3	3	1	1	18

Prior Treatment
Prior Treatment(Participants)	Group A (Steroids) - Cohort 1: 1x10(7)	Group A (Steroids) - Cohort 2: 3x10(7)	Group A (Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 1: 1x10(7)	Group B (No Steroids) - Cohort 2: 3x10(7)	Group B (No Steroids) - Cohort 3: 1x10(8)	Group B (No Steroids) - Cohort 4: 3x10(8)	Group B (No Steroids) - Cohort 5: 1x10(9)	Combined Steroids/no Steroids) - Cohort 6: 3x10(9)	Combined Steroids/no Steroids) - Cohort 7: 1x10(10)	Combined Steroids/no Steroids) - Cohort 8: 3-6x10(10)	Combined Steroids/no Steroids) - Cohort 9: 3x10(10)	Total
Surgery, radiation, temozolomide, bevacizumab,BCNU	1	0	0	0	0	0	0	0	0	0	0	0	1
Surgery, radiation, temozolomide, bevacizumab	0	1	0	1	0	0	0	1	0	0	0	0	3
Surgery, radiation, temozolomide	0	0	0	0	1	1	1	1	1	0	0	1	6
Radiation, temozolomide, bevacizumab	0	0	1	0	0	0	0	0	0	0	0	0	1
Surgery,radiation,temozolomide,bevacizumab,AZD7451	0	0	0	0	0	0	0	1	0	0	0	0	1
Surgery, radiation, temozolomide, veliparib, beva	0	0	0	0	0	0	0	0	1	0	0	0	1
Surg,rad,temozolomide,bevacizumab,EGFRvIII vaccine	0	0	0	0	0	0	0	0	1	0	0	0	1
Surgery, radiation, temozolomide, IMA950 vaccine	0	0	0	0	0	0	0	0	0	1	0	0	1
Surg,rad,temoz,EGFRvIIIvacc.vs.placebo tr,bev,treb	0	0	0	0	0	0	0	0	0	1	0	0	1
Surgery, radiation, temozolomide, carotuximab,beva	0	0	0	0	0	0	0	0	0	1	0	0	1
Surg,rad,temoz,EGFRvIIIvacc.vs.placebo trial,beva	0	0	0	0	0	0	0	0	0	0	1	0	1

Study locations

1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland 20892, United States

References and documents

Publications

FRANKEL SA, GERMAN WJ. Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg. 1958 Sep;15(5):489-503. doi: 10.3171/jns.1958.15.5.0489. No abstract available. PubMed 13576192 ↗
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. PubMed 15758009 ↗
Bloom HJ. Combined modality therapy for intracranial tumors. Cancer. 1975 Jan;35(1):111-20. doi: 10.1002/1097-0142(197501)35:13.0.co;2-#. PubMed 162849 ↗
Badhiwala J, Decker WK, Berens ME, Bhardwaj RD. Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 2013 Apr;13(4):405-24. doi: 10.1586/ern.13.23. PubMed 23545055 ↗
Morgan RA, Johnson LA, Davis JL, Zheng Z, Woolard KD, Reap EA, Feldman SA, Chinnasamy N, Kuan CT, Song H, Zhang W, Fine HA, Rosenberg SA. Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum Gene Ther. 2012 Oct;23(10):1043-53. doi: 10.1089/hum.2012.041. Epub 2012 Sep 24. PubMed 22780919 ↗

Study documents

Protocol and statistical analysis plan · Jun 28, 2018
Informed consent form · Jul 10, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 21, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01454596
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Steven Rosenberg, M.D. (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted: Oct 19, 2011
Start date: May 16, 2012
Primary completion: Nov 1, 2018
Completion: Jan 17, 2019
Results posted: Aug 21, 2019
Last update: Aug 21, 2019

Study contacts

Steven A Rosenberg, M.D.

principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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