Patients With Residual or Reccurent EGFRvIII+ GliomaPhase 1NCT02209376
Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
A Phase 1 study testing CART-EGFRvIII T cells in people with Patients With Residual or Reccurent EGFRvIII+ Glioma, run by University of Pennsylvania at 2 sites in United States.
Trial summary
An Open-Label Phase 1 Pilot Study to determine the safety and feasibility of CART-EGFRvIII (autologous T cells transduced with a lentiviral vector to express a chimeric antigen receptor specific for EGFRvIII) in the treatment of patients with EGFRvIII+ glioblastoma who have had their first recurrence as determined by… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Residual or Reccurent EGFRvIII+ Glioma
- What is being tested?
- CART-EGFRvIII T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Nov 2014to 4 Apr 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathological criteria: Glioblastoma (GBM) that is histologically confirmed by pathology review of surgically resected tissue.
- Tumor cells from resected tissue must be available for EGFRvIII testing. Patients who have previously been treated with an EGFRvIII-targeted therapy and recurred, must have a tumor sample obtained after their recurrence available for EGFRvIII testing.
- Age greater than 18 years.
- If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.
- ECOG performance status of 0 or 1 Documented negative serum HCG for female patients of child-bearing potential.
- Participants with adequate organ function as measured by:
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- White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 9.0 g/dL; without transfusion or growth factor support
- AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
- Serum creatinine less than or equal to 1.5 x upper limit of normal
- Coagulation tests PT and PTT have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
- Provide voluntary informed consent for Tissue Screening and Apheresis
- Subject met all Step 1 Eligibility Criteria.
- Tumor cells test positive for EGFRvIII expression (by RT-PCR, next generation sequencing, or immunohistochemistry) and a CART EGFRvIII product has been manufactured and formulated. Patients who have previously been treated with an EGFRvIII-targeted therapy and recurred are only eligible if a tumor sample obtained after their recurrence tests positive for EGFRvIII.
- Stage of disease:
- Cohort 1: Patients with first relapse of previously diagnosed primary glioblastoma. Recurrence may be determined by imaging and clinical criteria alone.
- Cohort 2: Patients with newly diagnosed glioblastoma with a less than 95% resection or greater than or equal to 1 cm^3 of residual disease on the post-operative MRI (typically post-operative day 1).
- If the patient is on dexamethasone, the dose must be 4 mg/day or less prior to CART-EGFRvIII infusion.
- It is anticipated that all patients in Cohort 2 will have completed standard of care external beam radiotherapy and chemotherapy with temozolomide (TMZ) at the time of the pre-infusion safety visit.
- Life expectancy less greater than 3 months
- ECOG performance status of 0 or 1
- 9. Participants with adequate organ function as measured by:
- White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 9.0 g/dL; without transfusion or growth factor support
- AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
- Serum creatinine less than or equal to 1.5 x upper limit of normal
- Coagulation tests PT and PTT have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.
- Adequate cardiac function (greater than EF 55%) 10. Provide voluntary informed consent for study treatment. 11. Female subjects of reproductive potential must agree to use a reliable method of contraception.
Who cannot join
- Female subjects of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.
- Uncontrolled active infection.
- Active or latent chronic hepatitis B [detectable hepatitis B surface antigen (HBsAg)] or active hepatitis C (positive serology [HCV Ab]) infection.
- HIV infection.
- Previous treatment with any gene therapy products.
- Known addiction to alcohol or illicit drugs.
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- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- Female subjects of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test within two weeks prior to CART-EGFRvIII cell infusion. The safety of this therapy on unborn children is not known.
- Uncontrolled active infection.
- Use of immunosuppressive agents such as cyclosporine, MMF, tacrolimus, or rapamycin within 4 weeks of enrollment on Step 2.
- A minimal dose of corticosteroid (dexamethasone up to 4 mg/day) is permitted. Recent or current use of inhaled steroids is not exclusionary.
- Previous treatment with any gene therapy products.
- Subjects or their physicians anticipate use of any of the following concurrent treatment or medications including: a. Radiosurgery (except for the Standard of Care Fractionated External Radiation therapy is a part of the protocol regimen in Cohort 2) b. Chemotherapy (except for the Standard of Care Temozolomide therapy in Cohort 2) c. Interferon (e.g. Intron-A®) d. Allergy desensitization injections e. Any ongoing investigational therapeutic medication. f. Bevacizumab
- Participants who have another cancer diagnosis with history of visceral metastases at the time of pre-entry evaluation. The following diagnoses are examples that will be allowed:
- squamous cell cancer of the skin without known metastasis
- basal cell cancer of the skin without known metastasis
- carcinoma in situ of the breast (DCIS or LCIS)
- carcinoma in situ of the cervix
- prostate cancer with only PSA recurrence
- any cancer that has not required systemic therapy (other than hormonal therapies) for the past three (3) years.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- Unstable angina and/or myocardial infarction within 6 months prior to screening
- Known addiction to alcohol or illicit drugs.
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
UCSF
San Francisco, California
About this study
Official title: Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
An Open-Label Phase 1 Pilot Study to determine the safety and feasibility of CART-EGFRvIII (autologous T cells transduced with a lentiviral vector to express a chimeric antigen receptor specific for EGFRvIII) in the treatment of patients with EGFRvIII+ glioblastoma who have had their first recurrence as determined by standard imaging or have have residual disease after initial resection.
- Being tested
- CART-EGFRvIII T cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART-EGFRvIII T cellsBiological
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Biological: CART-EGFRvIII T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2014 (estimated)
- Study start18 Nov 2014
- Primary completion4 Apr 2018
- Study completion4 Apr 2018
Why it stopped: Sponsor decision to terminate prior to completion to pursue combination therapies.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Patients With Residual or Reccurent EGFRvIII+ GliomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco
- Responsible party
- Sponsor
- Investigators
- Donald O'Rourke, MD, Principal investigator, Abramson Cancer Center at Penn MedicineSusan Chang, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02209376
- Sponsor's protocol ID
- UPCC 35313, 820381
- Status last verified
- Mar 2019
- First submitted
- 4 Aug 2014
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey SF, Navenot JM, Zheng Z, Levine BL, Okada H, June CH, Brogdon JL, Maus MV. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017 Jul 19;9(399):eaaa0984. doi: 10.1126/scitranslmed.aaa0984.
PubMed 28724573Tang OY, Tian L, Yoder T, Xu R, Kulikovskaya I, Gupta M, Melenhorst JJ, Lacey SF, O'Rourke DM, Binder ZA. PD1 Expression in EGFRvIII-Directed CAR T Cell Infusion Product for Glioblastoma Is Associated with Clinical Response. Front Immunol. 2022 May 6;13:872756. doi: 10.3389/fimmu.2022.872756. eCollection 2022.
PubMed 35603165Yin Y, Boesteanu AC, Binder ZA, Xu C, Reid RA, Rodriguez JL, Cook DR, Thokala R, Blouch K, McGettigan-Croce B, Zhang L, Konradt C, Cogdill AP, Panjwani MK, Jiang S, Migliorini D, Dahmane N, Posey AD Jr, June CH, Mason NJ, Lin Z, O'Rourke DM, Johnson LA. Checkpoint Blockade Reverses Anergy in IL-13Ralpha2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine Gliomas. Mol Ther Oncolytics. 2018 Aug 28;11:20-38. doi: 10.1016/j.omto.2018.08.002. eCollection 2018 Dec 21.
PubMed 30306125Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A, Boesteanu AC, Cogdill AP, Chen T, Fraietta JA, Kloss CC, Posey AD Jr, Engels B, Singh R, Ezell T, Idamakanti N, Ramones MH, Li N, Zhou L, Plesa G, Seykora JT, Okada H, June CH, Brogdon JL, Maus MV. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med. 2015 Feb 18;7(275):275ra22. doi: 10.1126/scitranslmed.aaa4963.
PubMed 25696001
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
- ClinicalTrials.gov ID
- NCT02209376
- Acronym / sponsor ID
- UPCC 35313, 820381
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to terminate prior to completion to pursue combination therapies.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- University of California, San Francisco
- Study start
- 18 Nov 2014 (actual)
- Primary completion
- 4 Apr 2018 (actual)
- Study completion
- 4 Apr 2018 (actual)
- First posted
- 5 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An Open-Label Phase 1 Pilot Study to determine the safety and feasibility of CART-EGFRvIII (autologous T cells transduced with a lentiviral vector to express a chimeric antigen receptor specific for EGFRvIII) in the treatment of patients with EGFRvIII+ glioblastoma who have had their first recurrence as determined by standard imaging or have have residual disease after initial resection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: CART-EGFRvIII T cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Pathological criteria: Glioblastoma (GBM) that is histologically confirmed by pathology review of surgically resected tissue.
- Tumor cells from resected tissue must be available for EGFRvIII testing. Patients who have previously been treated with an EGFRvIII-targeted therapy and recurred, must have a tumor sample obtained after their recurrence available for EGFRvIII testing.
- Age greater than 18 years.
- If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.
- ECOG performance status of 0 or 1 Documented negative serum HCG for female patients of child-bearing potential.
Key exclusion criteria (24 listed)
- Female subjects of reproductive potential who are pregnant or lactating. Female study participants of reproductive potential must have a negative serum pregnancy test as part of Step 1 eligibility confirmation.
- Uncontrolled active infection.
- Active or latent chronic hepatitis B [detectable hepatitis B surface antigen (HBsAg)] or active hepatitis C (positive serology [HCV Ab]) infection.
- HIV infection.
- Previous treatment with any gene therapy products.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CART-EGFRvIII T cells | Biological | Arm 1 |
Primary outcome
Number of adverse events
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Sponsor decision to terminate prior to completion to pursue combination therapies.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Results publication: PubMed 28724573O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey SF, Navenot JM, Zheng Z, Levine BL, Okada H, June CH, Brogdon JL, Maus MV. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017 Jul 19;9(399):eaaa0984. doi: 10.1126/scitranslmed.aaa0984.
- Derived from this study: PubMed 35603165Tang OY, Tian L, Yoder T, Xu R, Kulikovskaya I, Gupta M, Melenhorst JJ, Lacey SF, O'Rourke DM, Binder ZA. PD1 Expression in EGFRvIII-Directed CAR T Cell Infusion Product for Glioblastoma Is Associated with Clinical Response. Front Immunol. 2022 May 6;13:872756. doi: 10.3389/fimmu.2022.872756. eCollection 2022.
- Derived from this study: PubMed 30306125Yin Y, Boesteanu AC, Binder ZA, Xu C, Reid RA, Rodriguez JL, Cook DR, Thokala R, Blouch K, McGettigan-Croce B, Zhang L, Konradt C, Cogdill AP, Panjwani MK, Jiang S, Migliorini D, Dahmane N, Posey AD Jr, June CH, Mason NJ, Lin Z, O'Rourke DM, Johnson LA. Checkpoint Blockade Reverses Anergy in IL-13Ralpha2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine Gliomas. Mol Ther Oncolytics. 2018 Aug 28;11:20-38. doi: 10.1016/j.omto.2018.08.002. eCollection 2018 Dec 21.
- Derived from this study: PubMed 25696001Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A, Boesteanu AC, Cogdill AP, Chen T, Fraietta JA, Kloss CC, Posey AD Jr, Engels B, Singh R, Ezell T, Idamakanti N, Ramones MH, Li N, Zhou L, Plesa G, Seykora JT, Okada H, June CH, Brogdon JL, Maus MV. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med. 2015 Feb 18;7(275):275ra22. doi: 10.1126/scitranslmed.aaa4963.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald O'Rourke, MD principal investigator
Abramson Cancer Center at Penn Medicine
Susan Chang, MD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CART-EGFRvIII T cells in people with Patients With Residual or Reccurent EGFRvIII+ Glioma, run by University of Pennsylvania at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision to terminate prior to completion to pursue combination therapies.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02209376, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.