Stage IV Skin MelanomaPhase 1/2TCRNCT02654821
Study With T-cel Receptor Gene Therapy in Metastatic Melanoma
A Phase 1/2 study testing TCR transduced T-cells, Biopsy and Blood taking in people with Stage IV Skin Melanoma and Eye; Melanoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
Patients with stage IV melanoma (also eye melanoma) will be treated with TCR transduced cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Skin Melanoma, Eye; Melanoma
- What is being tested?
- TCR transduced T-cells, Biopsy and Blood taking
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2012to Jan 2020
- Phase
- Phase 1/2
- 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
- Patients must be ≥ 18 years of age.
- Patients must have inoperable stage IIIc or stage IV melanoma (AJCC), including ocular or mucosal melanoma, progressing after standard of care therapy, if available.
- Patients must be HLA-A*0201 positive.
- The primary tumor and/or metastasis have to be positive for MART-1 (>10% of tumor cells).
- Patients with measurable disease (RECIST 1.1)
- Patients must have a clinical performance status of ECOG 0 or 1.
- Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen.
- Patients must be able to understand and sign the Informed Consent document. Specific lab values
Who cannot join
- Life expectancy of less than three months.
- Requirement for systemic steroid therapy.
- Patients who have a history of CNS metastases.
- Patients with malignant pleural effusion or ascites.
- Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks.
- Patients who have: history of coronary revascularization, documented LVEF of less than 45%, clinically significant atrial and/or ventricular arrhythmias including but not limited to atrial fibrillation, ventricular tachycardia, 2° or 3° heart block, documented FEV1 less than or equal to 60% predicted for patients with a history of cigarette smoking (greater than 20 pack/year within the past 2 years) and with symptoms of respiratory distress
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- All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
- Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. A negative pregnancy test before inclusion in the trial is required for all women of child bearing potential.
- Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Antoni van Leeuwenhoek ziekenhuis
Amsterdam, North Holland, 1066CX
About this study
Official title: Multicenter Phase I/IIa Study Using T-cell Receptor Gene Therapy in Metastatic Melanoma
Patients with stage IV melanoma (also eye melanoma) will be treated with TCR transduced cells.
Read the detailed description
In this multicenter phase I/IIa trial 25 patients will be treated with non-myeloablative chemotherapy followed by adoptive transfer of autologous TCR transduced T cells, to study the feasibility, safety and efficacy of this treatment.
Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 or 30 mg/kg/day x 2 days i.v.) and fludarabine (25 mg/m2/day i.v. x 5 days). Following this regimen, patients will receive one single intravenous adoptive transfer of transduced T cells starting with the first dose level.
- Dose level 1: 5x10^7 transduced T cells, cyclophosphamide 60 mg/kg/day
- Dose level 1a: 1,0x10^8 transduced T cells, cyclophosphamide 30 mg/kg/day
- Dose level 2: 2,5x10^8 transduced T cells, cyclophosphamide 60 mg/kg/day
- Dose level 3: maximum 1x10^9 transduced T cells (depending on production yield). At time points 4, 8, and 12 weeks and every 3 months thereafter patients will be evaluated for response to treatment. After 3 patients have been treated in each dose level, but not before 8 weeks after the last patient has been infused with transduced T cells, the DSMB will be informed about the observed toxicity and efficacy within this cohort and decide, based on this information, whether the trial will be continued to the next dose level or will continue in the current dose level. The study will continue as the first stage (2-stage Simon), until a total of 16 patients have been enrolled and treated: if less than 2 responses are observed, the trial will be stopped and the conclusion will be that TCR lacks efficacy. Otherwise, the trial will continue its second stage. In addition, safety data after these first 16 patients will be evaluated by the DSMB. Any unexpected or serious (grade 3/4 or higher) toxicities during the trial, will be reported immediately to the DSMB and CCMO. Second stage: overall 25 patients will be enrolled (including the first stage): if the total number of responses for the two stages combined is less than 5, the trial will be stopped as soon as this is evident and the conclusion will be that TCR lacks efficacy.
- Conditions
- Stage IV Skin Melanoma, Eye; Melanoma
- Being tested
- TCR transduced T-cells, Biopsy, Blood taking
- Keywords
- Melanoma, TCR
- Medical subject headings
- Melanoma, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCR transduced T-cellsBiological
Eligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells.
BiopsyProcedure or surgery
During screening, after treatment and at time of regression/progression a biopsy will be taken for translational research.
Blood takingProcedure or surgery
During screening, after the infusion with T-cells, after treatment and at time of regression/progression blood will be taken for translational research.
| Study group | Role | What they receive |
|---|---|---|
| TCR treatment | Experimental | Eligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells. Receives: Biological: TCR transduced T-cells; Procedure: Biopsy; Procedure: Blood taking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of the TCR treatment (according to CTCAE 4.0)
Safety of the TCR treatment will be measured by noting the toxicity (according to CTCAE 4.0) that the patient experiences while on treatment.
Measured: Baseline until release from the hospital, about 4 weeks.
Objective response rate according to RECIST 1.1.
The objective response rate will be measured by RECIST 1.1.
Measured: Baseline until progressive disease, median 6 months.
Secondary outcomes (4)
1-year progression free survival (PFS)
1-year PFS will we measured by the number of patients still free of disease after 1 year, using RECIST 1.1 to measure progressive disease
Measured: Baseline until 1 year after treatment.
Efficacy of induction of tumor specific T cell responses as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples
Efficacy of induction of tumor specific T cell responses as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples at several time points following adoptive transfer and in tumor biopsies when possible.
Measured: Baseline until progressive disease, median 6 months.
Overall survival
Measured: Assessed up to 12 months
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline
To study whether the infusion of MART-1 specific TCR (1D3 HMCys) transduced T cells will lead to systemic release of inflammatory cytokines.
Measured: Baseline until progressive disease, median 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study startMar 2012
- Primary completionOct 2019 (estimated)
- Study completionJan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Skin MelanomaStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John B.A.G. Haanen, Prof., Principal investigator, Antoni van Leeuwenhoek Ziekenhuis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654821
- Sponsor's protocol ID
- M11TCR
- Acronym
- TCR
- Status last verified
- Oct 2018
- First submitted
- 8 Jan 2016
- Last updated
- 2 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase I/IIa Study Using T-cell Receptor Gene Therapy in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02654821
- Acronym / sponsor ID
- TCR / M11TCR
- Conditions
- Stage IV Skin Melanoma, Eye; Melanoma
- Keywords
- Melanoma, TCR
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- Mar 2012 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 13 Jan 2016 (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.
Patients with stage IV melanoma (also eye melanoma) will be treated with TCR transduced cells.
Detailed description
In this multicenter phase I/IIa trial 25 patients will be treated with non-myeloablative chemotherapy followed by adoptive transfer of autologous TCR transduced T cells, to study the feasibility, safety and efficacy of this treatment.
Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 or 30 mg/kg/day x 2 days i.v.) and fludarabine (25 mg/m2/day i.v. x 5 days). Following this regimen, patients will receive one single intravenous adoptive transfer of transduced T cells starting with the first dose level.
- Dose level 1: 5x10^7 transduced T cells, cyclophosphamide 60 mg/kg/day
- Dose level 1a: 1,0x10^8 transduced T cells, cyclophosphamide 30 mg/kg/day
- Dose level 2: 2,5x10^8 transduced T cells, cyclophosphamide 60 mg/kg/day
- Dose level 3: maximum 1x10^9 transduced T cells (depending on production yield). At time points 4, 8, and 12 weeks and every 3 months thereafter patients will be evaluated for response to treatment. After 3 patients have been treated in each dose level, but not before 8 weeks after the last patient has been infused with transduced T cells, the DSMB will be informed about the observed toxicity and efficacy within this cohort and decide, based on this information, whether the trial will be continued to the next dose level or will continue in the current dose level. The study will continue as the first stage (2-stage Simon), until a total of 16 patients have been enrolled and treated: if less than 2 responses are observed, the trial will be stopped and the conclusion will be that TCR lacks efficacy. Otherwise, the trial will continue its second stage. In addition, safety data after these first 16 patients will be evaluated by the DSMB. Any unexpected or serious (grade 3/4 or higher) toxicities during the trial, will be reported immediately to the DSMB and CCMO. Second stage: overall 25 patients will be enrolled (including the first stage): if the total number of responses for the two stages combined is less than 5, the trial will be stopped as soon as this is evident and the conclusion will be that TCR lacks efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCR treatment | Experimental | Biological: TCR transduced T-cells, Procedure: Biopsy, Procedure: Blood takingEligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must be ≥ 18 years of age.
- Patients must have inoperable stage IIIc or stage IV melanoma (AJCC), including ocular or mucosal melanoma, progressing after standard of care therapy, if available.
- Patients must be HLA-A*0201 positive.
- The primary tumor and/or metastasis have to be positive for MART-1 (>10% of tumor cells).
- Patients with measurable disease (RECIST 1.1)
Key exclusion criteria (9 listed)
- Life expectancy of less than three months.
- Requirement for systemic steroid therapy.
- Patients who have a history of CNS metastases.
- Patients with malignant pleural effusion or ascites.
- Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks.
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 |
|---|---|---|
| TCR transduced T-cellsEligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells. | Biological | TCR treatment |
| BiopsyDuring screening, after treatment and at time of regression/progression a biopsy will be taken for translational research. | Procedure or surgery | TCR treatment |
| Blood takingDuring screening, after the infusion with T-cells, after treatment and at time of regression/progression blood will be taken for translational research. | Procedure or surgery | TCR treatment |
Primary outcome
Safety of the TCR treatment (according to CTCAE 4.0)
Time frame: Baseline until release from the hospital, about 4 weeks.
Safety of the TCR treatment will be measured by noting the toxicity (according to CTCAE 4.0) that the patient experiences while on treatment.
Objective response rate according to RECIST 1.1.
Time frame: Baseline until progressive disease, median 6 months.
The objective response rate will be measured by RECIST 1.1.
4 secondary outcomes
1-year progression free survival (PFS)
Time frame: Baseline until 1 year after treatment.
Efficacy of induction of tumor specific T cell responses as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples
Time frame: Baseline until progressive disease, median 6 months.
Overall survival
Time frame: Assessed up to 12 months
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline
Time frame: Baseline until progressive disease, median 6 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2018.
- Individual participant dataSharing planned: Undecided
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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.
John B.A.G. Haanen, Prof. principal investigator
Antoni van Leeuwenhoek Ziekenhuis
1 site 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 TCR transduced T-cells, Biopsy and Blood taking in people with Stage IV Skin Melanoma and Eye; Melanoma, run by The Netherlands Cancer Institute at 1 site in Netherlands.
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 8 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
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?
Safety of the TCR treatment (according to CTCAE 4.0) (time frame: Baseline until release from the hospital, about 4 weeks.). The study lists 2 primary outcomes in all. 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 2 Nov 2018.