Ovarian CancerPhase 1/2NCT01567891
CT Antigen TCR-redirected T Cells for Ovarian Cancer.
A Phase 1/2 study testing NYESO-1c259 T cells in people with Ovarian Cancer, run by Adaptimmune at 5 sites in United States.
Trial summary
This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- NYESO-1c259 T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Jul 2013to 6 Jun 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Must have a diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum resistant disease and/or have received ≥ 2 lines of chemotherapy
- Age ≥ 18 years of age
- No significant immunodeficiency
- Have been informed of other treatment options
- Must be HLA A*0201, HLA-A*0205, and/or HLA-A*0206 positive by high resolution testing.
- Patient's tumor must be positive by histological assay for NY-ESO-1ᶜ²⁵⁹T, according to the screening algorithm as described in Section 3.3.1. Positive expression is defined as ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry
Show all 27Show fewer
- ECOG performance status of 0 or 1
- Life expectancy of > 4 months
- Prior therapies:
- prior immunotherapy, or prior investigational agents should be washed out 4 weeks before apheresis and must be completed 4 weeks prior to pre-infusion lymphodepletive chemotherapy.
- monoclonal antibody therapy must be completed at least 6 weeks prior to pre-infusion lymphodepletive chemotherapy
- All previous cytotoxic chemotherapy, monoclonal antibody therapy, immune therapy should be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
- Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy
- Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week before apheresis and must be completed at least 1 week prior to pre-infusion lymphodepletive chemotherapy.
- Any grade 3 or 4 -hematologic toxicity of previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
- Must have measurable disease as defined by RECIST 1.1.
- Must have adequate venous access for apheresis.
- Women of childbearing potential are requested to use acceptable methods of birth control for the duration of the study and until persistence of the study drug is no longer detected in the patient. This may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception. It is recommended that a combination of two methods be used.
- Patients must have normal organ and marrow function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute Neutrophil Count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 ULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- creatinine ≤ 2.0 mg/dL OR
- creatinine clearance > 60 mL/min for patients with creatinine levels above institutional normal
- Patient must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
Who cannot join
- Currently receiving any other investigational agents
- Patients with active brain metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study
- Prior malignancy (except non-melanoma skin cancer) within 18 months of study entry NOTE: Patients must be in complete remission from prior malignancy in order to be eligible to enter the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g. interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to study entry. NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects are prescribed a brief course of oral corticosteroids, the use should be limited to less than 7 days. Use of steroids before apheresis and immune assessment blood draws should be discouraged as it will affect white blood cell function.
Show all 11Show fewer
- Active infection with HIV, HBV or HCV
- Receipt of an experimental vaccine within 2 months or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months, or has received any previous gene therapy using an integrating vector
- History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
- Lack of availability of a patient for immunological and clinical follow-up assessment
- Evidence or history of significant cardiac disease
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
City of Hope National Medical Center
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Stanford Cancer Institute
Stanford, California, 94305
About this study
Official title: A Phase I/IIa, Open Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Patients With Recurrent or Treatment Refractory Ovarian Cancer.
This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.
Read the detailed description
This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1ᶜ²⁵⁹T. The trial is conducted entirely with outpatient procedures; however, patients may be hospitalized for the cytoreductive chemotherapy at the discretion of the investigator. Upon enrollment, patients will undergo leukapheresis for T cell collection, and their cells will be genetically engineered and expanded ex vivo. Seven days prior to receiving T-cells patients will undergo a cyclophosphamide conditioning regimen to potentiate the immunotherapy. The cell product will be infused as a single infusion (Day 0, typically Monday) to mitigate risks associated with unanticipated infusion reactions. Patients will be followed daily for the first week, weekly until 4 weeks, 8 weeks, and 12 weeks and then at 6 months and every 3 months until disease progression. Patients will undergo disease monitoring by MRI/CT scan (as appropriate for disease) at baseline, day 28, 8 weeks and 12 weeks, and months 6, and every 3 months until progression. Tumor biopsies will be taken at baseline, Week 8, and upon progression. In patients who have progressive disease following initial infusion but whose tumors continue to express NY-ESO-1, these patients may be eligible for a second infusion with redirected T cells. At disease progression, the interventional portion of the protocol ends and long term follow-up (LTFU) begins, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.
- Conditions
- Ovarian Cancer
- Being tested
- NYESO-1c259 T cells
- Keywords
- Ovarian Cancer, Cell Therapy, T Cell Therapy, NY-ESO-1, Immuno-oncology, Metastatic, Previously treated, T Cell Receptor
- Medical subject headings
- Ovarian Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NYESO-1c259 T cellsBiological
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Patients will receive at least 1x10⁹ transduced cells, however the target dose for this protocol is for patients to receive 5x10⁹ transduced cells with a maximum possible dose of 6x10⁹ administered as a single intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NYESO-1c259 T cells. Receives: Biological: NYESO-1c259 T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Related to Study Treatment
Number of Participants with Adverse Events related to study treatment
Measured: Up to 12 months
Secondary outcomes (4)
Tumor Response
Number of participants with response as assessed by Immune-related Response Criteria (irRC)
Measured: Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression
Peak Persistence of Modified T-cells in the Peripheral Blood
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
Measured: Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU
Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood.
Percentage of CD4+pentamer+ or CD8+pentamer+ cells expressing LAG-3, PD-1, TIM-3 in the functionality of NY-ESO-1ᶜ²⁵⁹T cells in the manufactured product and post-treatment blood.
Measured: Weeks 4 and 8 post T-cell infusion
Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein
NY-ESO-1 expression as determined by Histoscore (H score). Histoscore (0-300) represents the amount of NY-ESO-1 protein present in the tissue sample.
H-Score formula:
[1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]
(It is not clearly established if NY-ESO-1 H score has an association with prognosis.)
Measured: Screening and at Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2012 (estimated)
- Study start9 Jul 2013
- Primary completion6 Jun 2017
- Study completion6 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adaptimmune
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kunle Odunsi, MD, PhD, Study chair, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01567891
- Sponsor's protocol ID
- ADP-0011-001
- Other IDs
- 230612
- Status last verified
- Dec 2018
- First submitted
- 16 Mar 2012
- Last updated
- 27 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Open Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Patients With Recurrent or Treatment Refractory Ovarian Cancer.
- ClinicalTrials.gov ID
- NCT01567891
- Acronym / sponsor ID
- ADP-0011-001
- Conditions
- Ovarian Cancer
- Keywords
- Ovarian Cancer, Cell Therapy, T Cell Therapy, NY-ESO-1, Immuno-oncology, Metastatic, Previously treated, T Cell Receptor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- AdaptimmuneIndustry (pharma, biotech, devices)
- Study start
- 9 Jul 2013 (actual)
- Primary completion
- 6 Jun 2017 (actual)
- Study completion
- 6 Jun 2017 (actual)
- First posted
- 30 Mar 2012 (estimated)
- Results
- Posted 3 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.
Detailed description
This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NY-ESO-1ᶜ²⁵⁹T. The trial is conducted entirely with outpatient procedures; however, patients may be hospitalized for the cytoreductive chemotherapy at the discretion of the investigator. Upon enrollment, patients will undergo leukapheresis for T cell collection, and their cells will be genetically engineered and expanded ex vivo. Seven days prior to receiving T-cells patients will undergo a cyclophosphamide conditioning regimen to potentiate the immunotherapy. The cell product will be infused as a single infusion (Day 0, typically Monday) to mitigate risks associated with unanticipated infusion reactions. Patients will be followed daily for the first week, weekly until 4 weeks, 8 weeks, and 12 weeks and then at 6 months and every 3 months until disease progression. Patients will undergo disease monitoring by MRI/CT scan (as appropriate for disease) at baseline, day 28, 8 weeks and 12 weeks, and months 6, and every 3 months until progression. Tumor biopsies will be taken at baseline, Week 8, and upon progression. In patients who have progressive disease following initial infusion but whose tumors continue to express NY-ESO-1, these patients may be eligible for a second infusion with redirected T cells. At disease progression, the interventional portion of the protocol ends and long term follow-up (LTFU) begins, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: NYESO-1c259 T cellsThis is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NYESO-1c259 T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Must have a diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum resistant disease and/or have received ≥ 2 lines of chemotherapy
- Age ≥ 18 years of age
- No significant immunodeficiency
- Have been informed of other treatment options
- Must be HLA A*0201, HLA-A*0205, and/or HLA-A*0206 positive by high resolution testing.
Key exclusion criteria (11 listed)
- Currently receiving any other investigational agents
- Patients with active brain metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study
- Prior malignancy (except non-melanoma skin cancer) within 18 months of study entry NOTE: Patients must be in complete remission from prior malignancy in order to be eligible to enter the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| NYESO-1c259 T cellsCytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Patients will receive at least 1x10⁹ transduced cells, however the target dose for this protocol is for patients to receive 5x10⁹ transduced cells with a maximum possible dose of 6x10⁹ administered as a single intravenous (IV) infusion. | Biological | Cohort 1 |
Primary outcome
Adverse Events Related to Study Treatment
Time frame: Up to 12 months
Number of Participants with Adverse Events related to study treatment
4 secondary outcomes
Tumor Response
Time frame: Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression
Peak Persistence of Modified T-cells in the Peripheral Blood
Time frame: Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU
Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood.
Time frame: Weeks 4 and 8 post T-cell infusion
Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein
Time frame: Screening and at Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Ovarian Cancer
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Recruiting
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer
Ovarian Carcinoma
RecruitingPhase 2
Investigation of Ubamatamab Combination Therapy in Adult Participants With Platinum-Resistant Ovarian Cancer
Ovarian Cancer, Fallopian Tube Cancer
Active, not recruitingPhase 1/2
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Colorectal Neoplasms, Breast Neoplasms
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
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.
Kunle Odunsi, MD, PhD study chair
Roswell Park Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NYESO-1c259 T cells in people with Ovarian Cancer, run by Adaptimmune at 5 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 27 inclusion and 11 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: finished, as of the sponsor's last update on 27 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Adverse Events Related to Study Treatment (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2019.