MelanomaPhase 1/2NCT01350401
Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma
A Phase 1/2 study testing Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T in people with Melanoma, run by Adaptimmune at 2 sites in United States.
Trial summary
The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jun 2011to 1 Mar 2018
- 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
- Patients must have histologically or cytologically confirmed melanoma stage III/IV, unresectable
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan
- One prior cytotoxic therapy for the treatment of metastatic disease is allowed. Unlimited regimens using biological agents (vaccines), immunotherapy, or targeted agents is permitted. For example, BRAF inhibitors and ipilimumab are permitted. Patients must have fully recovered from the acute toxicities related to any prior therapy. Prior therapy must be completed ≥28 days before the first dose of cyclophosphamide.
- Age ≥18
- Life expectancy of greater than 3 months
- ECOG performance status ≤ 1
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- Patients must have normal organ and marrow function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute Neutrophil Count (ANC) ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- Creatinine ≤ 2.0 mg/dl Or Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- The patient must express HLA class I allele HLA-A*0201 for NY-ESO-1/LAGE.
- Patient must have proven positive tumor sample for NY-ESO-1 as determined by an H score for immunohistochemistry staining. Positive expression is defined as an H score ≥ 100 where the H score = [2 x (% cells 2+) + 3 x (% cells 3+)].
- NOTE: The percentages of negative or weakly stained nuclei (i.e. 1+) are not to be included in the calculation of the H score.
- Female subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study.
- Ability of the patient (or legally authorized representative if applicable) to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
- Patients may not be receiving any other investigational agents.
- Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study.
- Active infection
- Prior malignancy (except non-melanoma skin cancer) within 3 years.
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- 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. All patients will undergo a cardiac stress test for evaluation of cardiac function.
- Pregnant or nursing females
- Active infection with HIV, HBV or HCV as defined below, due to the immunosuppressive effects of cyclophosphamide used and the unknown risks associated with viral replication.
- Positive serology for HIV
- Active Hepatitis B infection as determined by test for hepatitis B surface antigen.
- Active Hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV RNA by any RT-PCR or bDNA assay must be performed at screening by a local laboratory with a CLIA certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Yale School of Medicine
New Haven, Connecticut, 06520
Washington University in St. Louis
St Louis, Missouri, 63110
About this study
The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.
Read the detailed description
Purpose of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target melanoma cells rather than their usual target. Study subjects must have histologically or cytologically melanoma stage 3/4 and their tumor must express HLA Class 1 allele HLA-A*0201 for NY-ESO-1/LAGE. Subjects must also have measureable disease on study entry, as defined by at least one lesion that can be measured in at least one dimension >= 10mm with spiral CT scan.
- Conditions
- Melanoma
- Being tested
- Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T
- Keywords
- Melanoma, Cell Therapy, T Cell Therapy, NY-ESO-1, Immuno-oncology, Metastatic, Previously treated, T Cell Receptor
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹TGenetic
Cytoreductive chemotherapy followed by infusion of NY-ESO-1ᶜ²⁵⁹T
| Study group | Role | What they receive |
|---|---|---|
| NY-ESO-1/LAGE-1 and HLA-A*02 Positive Subjects | Experimental | Not described Receives: Genetic: Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T |
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 NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3
Measured: Up to 12 months
Secondary outcomes (3)
Tumor Response
Number of participants with response as assessed by RECIST (version 1.1) criteria.
Measured: Change from Baseline, every 4 weeks until Month 5 and then every other month through Month 11
Determine the Functional Properties and Phenotype of Modified T-cells From Peripheral Blood and Tumor Sites.
Measurement of functionality of NY-ESO-1ᶜ²⁵⁹T cells in the blood and tumor sites.
Measured: 8 Weeks post T-cell infusion
Peak Persistence of Modified T-cells in the Peripheral Blood
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)
Measured: Days 1, 5-9, 12-16, weekly thereafter through Week 12, monthly thereafter through Month 12, and during LTFU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2011 (estimated)
- Study start1 Jun 2011
- Primary completion17 Feb 2016
- Study completion1 Mar 2018
Why it stopped: Lack of enrollment
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 MelanomaStudies 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adaptimmune
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gerald P Linette, MD, PhD, Principal investigator, Washington University School of MedicineHarriet Kluger, MD, Principal investigator, Yale New Haven Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01350401
- Sponsor's protocol ID
- ADP 01611
- Status last verified
- Jan 2019
- First submitted
- 2 May 2011
- Last updated
- 10 Jan 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 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01350401
- Acronym / sponsor ID
- ADP 01611
- Conditions
- Melanoma
- Keywords
- Melanoma, 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
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- AdaptimmuneIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2011 (actual)
- Primary completion
- 17 Feb 2016 (actual)
- Study completion
- 1 Mar 2018 (actual)
- First posted
- 9 May 2011 (estimated)
- Results
- Posted 8 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.
Detailed description
Purpose of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target melanoma cells rather than their usual target. Study subjects must have histologically or cytologically melanoma stage 3/4 and their tumor must express HLA Class 1 allele HLA-A*0201 for NY-ESO-1/LAGE. Subjects must also have measureable disease on study entry, as defined by at least one lesion that can be measured in at least one dimension >= 10mm with spiral CT scan.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NY-ESO-1/LAGE-1 and HLA-A*02 Positive Subjects | Experimental | Genetic: Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed melanoma stage III/IV, unresectable
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan
- One prior cytotoxic therapy for the treatment of metastatic disease is allowed. Unlimited regimens using biological agents (vaccines), immunotherapy, or targeted agents is permitted. For example, BRAF inhibitors and ipilimumab are permitted. Patients must have fully recovered from the acute toxicities related to any prior therapy. Prior therapy must be completed ≥28 days before the first dose of cyclophosphamide.
- Age ≥18
- Life expectancy of greater than 3 months
Key exclusion criteria (12 listed)
- Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
- Patients may not be receiving any other investigational agents.
- Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study.
- Active infection
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 |
|---|---|---|
| Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹TCytoreductive chemotherapy followed by infusion of NY-ESO-1ᶜ²⁵⁹T | Genetic | NY-ESO-1/LAGE-1 and HLA-A*02 Positive Subjects |
Primary outcome
Adverse Events Related to Study Treatment
Time frame: Up to 12 months
Number of Participants with NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3
3 secondary outcomes
Tumor Response
Time frame: Change from Baseline, every 4 weeks until Month 5 and then every other month through Month 11
Determine the Functional Properties and Phenotype of Modified T-cells From Peripheral Blood and Tumor Sites.
Time frame: 8 Weeks post T-cell infusion
Peak Persistence of Modified T-cells in the Peripheral Blood
Time frame: Days 1, 5-9, 12-16, weekly thereafter through Week 12, monthly thereafter through Month 12, and during LTFU
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Gerald P Linette, MD, PhD principal investigator
Washington University School of Medicine
Harriet Kluger, MD principal investigator
Yale New Haven Hospital
2 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 Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T in people with Melanoma, run by Adaptimmune 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 18 inclusion and 12 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 10 Jan 2019. 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 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 8 May 2018). 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 10 Jan 2019.