Melanoma (Skin)Phase 1NCT00512889
Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma
A Phase 1 study testing therapeutic autologous lymphocytes, Use of an artificial antigen presenting cell (aAPC) to generate CTL and GM-CSF in people with Melanoma (Skin), run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- therapeutic autologous lymphocytes, Use of an artificial antigen presenting cell (aAPC) to generate CTL and GM-CSF
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Jan 2013
- 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
- Patients with metastatic melanoma: Either unresectable Stage III or any Stage IV
- ECOG of 0 or 1
- HLA-A*0201 haplotype
- Baseline tumor biopsy MART1/Melan-A expression present (in >10% of tumor cells)
- Patient provides consent for all required biopsies
- Adequate intravenous access for leukapheresis
Show all 9Show fewer
- Absolute lymphocyte count >500/ul at least once within 30 days of leukapheresis
- Life expectancy greater than 4 months in the opinion of the study clinician
- Negative pregnancy test
Who cannot join
- Administration of systemic corticosteroids within 28 days of planned leukapheresis
- Administration of cytotoxic chemotherapy or anti-tumor immunotherapy within 28 days of planned leukapheresis
- Administration of radiotherapy within 28 days of planned leukapheresis with the exception of subjects accrued to Cohort 3
- Active autoimmunity requiring systemic immunosuppressive therapy
- HIV infection
- Previous enrollment on this protocol and infusion of MART1/Melan-A CTL
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Pilot Study of the Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma
RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer.
PURPOSE: This early phase trial is studying the feasibility and side effects of intravenous infusions of CTL generated in the laboratory. To produce the CTL, the study participant's own immune cells are collected by a procedure called a leukapheresis. The cells then undergo laboratory processing for three weeks. Part of this processing includes mixing the patients immune cells with a new kind of cell that has some extra genes added to it. These extra genes are to "teach" the participant's own immune cells to become anti-tumor CTL that can attack the melanoma.
Read the detailed description
DETAILED OUTLINE: This is an early phase pilot/feasibility trial.
Study subjects will be sequentially accrued to three cohorts. Cohorts 1 and 2 will evaluate the safety and feasibility of infusing two different doses of CTL.
- Participants in all cohorts will undergo two CTL infusions 5 weeks apart.
- Procedures performed during the trial will include physical examinations, laboratory tests, delayed hypersensitivity testing, and skin biopsies.
- Between 5 and 8 days after the first CTL infusion, a biopsy or excision of a melanoma lesion may be performed.
- Three leukapheresis procedures will be performed: two to collect peripheral blood for CTL production and one for research purposes at the end of the clinical trial.
- Radiology tests (including CT scans) will be performed prior to infusion and about 4-5 weeks after the second CTL infusion.
- Conditions
- Melanoma (Skin)
- Being tested
- therapeutic autologous lymphocytes, Use of an artificial antigen presenting cell (aAPC) to generate CTL, GM-CSF, Irradiation of cutaneous tumor lesion
- Keywords
- CTL, MART-1, Melan-A, artificial APC, melanoma, metastatic melanoma, adoptive immunotherapy, adoptive cell transfer, immunotherapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic autologous lymphocytesBiological
Autologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC.
Use of an artificial antigen presenting cell (aAPC) to generate CTLGenetic
A genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL.
GM-CSFDrug
GM-CSF will be used as an immune activator and combined with the infusion of MART1/Melan-A specific CTL.
Irradiation of cutaneous tumor lesionRadiation
Irradiation of cutaneous melanoma lesion will be combined with the infusion of MART1/Melan-A specific CTL.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Different dose of CTL Receives: Biological: therapeutic autologous lymphocytes; Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL |
| Cohort 2 | Experimental | Different dose of CTL Receives: Biological: therapeutic autologous lymphocytes; Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL |
| Cohort 3 | Experimental | Combination of CTL with GMCSF +/- radiation Receives: Biological: therapeutic autologous lymphocytes; Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL; Drug: GM-CSF; Radiation: Irradiation of cutaneous tumor lesion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population
Measured: 2 years
Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines
Measured: 2 years
Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
Measured: 2 years
Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
Measured: 2 years
Secondary outcomes (1)
Evaluate function, phenotype, and trafficking of infused CTL.
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 posted8 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionFeb 2011
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by Dana-Farber 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcus O. Butler, MD, Dana-Farber Cancer Institute
- Investigators
- Marcus Butler, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512889
- Sponsor's protocol ID
- 06-250
- Status last verified
- Feb 2013
- First submitted
- 3 Aug 2007
- Last updated
- 1 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Butler MO, Friedlander P, Milstein MI, Mooney MM, Metzler G, Murray AP, Tanaka M, Berezovskaya A, Imataki O, Drury L, Brennan L, Flavin M, Neuberg D, Stevenson K, Lawrence D, Hodi FS, Velazquez EF, Jaklitsch MT, Russell SE, Mihm M, Nadler LM, Hirano N. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells. Sci Transl Med. 2011 Apr 27;3(80):80ra34. doi: 10.1126/scitranslmed.3002207.
PubMed 21525398
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma
- ClinicalTrials.gov ID
- NCT00512889
- Acronym / sponsor ID
- 06-250
- Conditions
- Melanoma (Skin)
- Keywords
- CTL, MART-1, Melan-A, artificial APC, melanoma, metastatic melanoma, adoptive immunotherapy, adoptive cell transfer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- Aug 2007
- Primary completion
- Feb 2011 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 8 Aug 2007 (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.
RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer.
PURPOSE: This early phase trial is studying the feasibility and side effects of intravenous infusions of CTL generated in the laboratory. To produce the CTL, the study participant's own immune cells are collected by a procedure called a leukapheresis. The cells then undergo laboratory processing for three weeks. Part of this processing includes mixing the patients immune cells with a new kind of cell that has some extra genes added to it. These extra genes are to "teach" the participant's own immune cells to become anti-tumor CTL that can attack the melanoma.
Detailed description
DETAILED OUTLINE: This is an early phase pilot/feasibility trial.
Study subjects will be sequentially accrued to three cohorts. Cohorts 1 and 2 will evaluate the safety and feasibility of infusing two different doses of CTL.
- Participants in all cohorts will undergo two CTL infusions 5 weeks apart.
- Procedures performed during the trial will include physical examinations, laboratory tests, delayed hypersensitivity testing, and skin biopsies.
- Between 5 and 8 days after the first CTL infusion, a biopsy or excision of a melanoma lesion may be performed.
- Three leukapheresis procedures will be performed: two to collect peripheral blood for CTL production and one for research purposes at the end of the clinical trial.
- Radiology tests (including CT scans) will be performed prior to infusion and about 4-5 weeks after the second CTL infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: therapeutic autologous lymphocytes, Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTLDifferent dose of CTL |
| Cohort 2 | Experimental | Biological: therapeutic autologous lymphocytes, Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTLDifferent dose of CTL |
| Cohort 3 | Experimental | Biological: therapeutic autologous lymphocytes, Genetic: Use of an artificial antigen presenting cell (aAPC) to generate CTL, Drug: GM-CSF, Radiation: Irradiation of cutaneous tumor lesionCombination of CTL with GMCSF +/- radiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with metastatic melanoma: Either unresectable Stage III or any Stage IV
- ECOG of 0 or 1
- HLA-A*0201 haplotype
- Baseline tumor biopsy MART1/Melan-A expression present (in >10% of tumor cells)
- Patient provides consent for all required biopsies
Key exclusion criteria (6 listed)
- Administration of systemic corticosteroids within 28 days of planned leukapheresis
- Administration of cytotoxic chemotherapy or anti-tumor immunotherapy within 28 days of planned leukapheresis
- Administration of radiotherapy within 28 days of planned leukapheresis with the exception of subjects accrued to Cohort 3
- Active autoimmunity requiring systemic immunosuppressive therapy
- HIV 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 |
|---|---|---|
| therapeutic autologous lymphocytesAutologous CTL generated from peripheral blood following culture with MART1/Melan-A peptide pulsed aAPC. | Biological | Cohort 1, Cohort 2, Cohort 3 |
| Use of an artificial antigen presenting cell (aAPC) to generate CTLA genetically modified artificial antigen presenting cell (aAPC) is used in the generation of anti-tumor CTL. | Genetic | Cohort 1, Cohort 2, Cohort 3 |
| GM-CSFGM-CSF will be used as an immune activator and combined with the infusion of MART1/Melan-A specific CTL. | Drug | Cohort 3 |
| Irradiation of cutaneous tumor lesionIrradiation of cutaneous melanoma lesion will be combined with the infusion of MART1/Melan-A specific CTL. | Radiation | Cohort 3 |
Primary outcome
Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population
Time frame: 2 years
Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines
Time frame: 2 years
Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
Time frame: 2 years
Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
Time frame: 2 years
1 secondary outcome
Evaluate function, phenotype, and trafficking of infused CTL.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2013.
- Results publication: PubMed 21525398Butler MO, Friedlander P, Milstein MI, Mooney MM, Metzler G, Murray AP, Tanaka M, Berezovskaya A, Imataki O, Drury L, Brennan L, Flavin M, Neuberg D, Stevenson K, Lawrence D, Hodi FS, Velazquez EF, Jaklitsch MT, Russell SE, Mihm M, Nadler LM, Hirano N. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells. Sci Transl Med. 2011 Apr 27;3(80):80ra34. doi: 10.1126/scitranslmed.3002207.
Related trials for Melanoma (Skin)
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
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.
Marcus Butler, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing therapeutic autologous lymphocytes, Use of an artificial antigen presenting cell (aAPC) to generate CTL and GM-CSF in people with Melanoma (Skin), run by Dana-Farber Cancer Institute at 1 site 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 9 inclusion and 6 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 1 Mar 2013. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population (time frame: 2 years). The study lists 4 primary outcomes in all. 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 NCT00512889, which also lists 1 linked publication.
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 1 Mar 2013.