MelanomaPhase 1MARVSmALoNCT02482532
Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma
A Phase 1 study testing tvs-CTL Vaccine in people with Melanoma, run by Gary Doolittle at 1 site in United States.
Trial summary
The researchers will investigate if modified T-cells from a patients own system can be utilized to find and destroy metastatic melanoma tumor and thus improve patient outcomes. Read more about this study
- Who is it for?
- Ages 18 to 66 years
- Conditions the study is for
- Melanoma
- What is being tested?
- tvs-CTL Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2016to 13 Sep 2021
- 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 to 66 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
- Life expectancy of at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
- Laboratory Values
- absolute neutrophil count > 500 microliters (mcL)
- platelet > 50,000 mcL
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- serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal (IULN)
- total bilirubin < 3 x IULN
- serum creatinine < 3 x IULN
- Pulse oximetry of > 95% on room air.
- Must have recovered from the toxic effects of all prior chemotherapy
Who cannot join
- Patients with rapidly progressive disease.
- Patient is currently receiving any investigational drugs
- Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
- Patients must not have tumor in a location where enlargement could cause airway obstruction
- Patient is pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products.
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- Currently receiving immunosuppressive drugs such as corticosteroids (excluding topical treatment), tacrolimus or cyclosporin
- Received any tumor vaccines within previous six weeks
- Known hypersensitivity to rat monoclonal antibodies
- History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus, Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).
- Allergy to baker's yeast or other components of the vaccines.
- History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B
- History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a cause other than the vaccine was indicated.
- Melanoma involvement of the central nervous system
- Chemotherapy given within the last 28 days
- Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma
The researchers will investigate if modified T-cells from a patients own system can be utilized to find and destroy metastatic melanoma tumor and thus improve patient outcomes.
Read the detailed description
The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.
The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.
The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.
- Conditions
- Melanoma
- Being tested
- tvs-CTL Vaccine
- Keywords
- Melanoma, metastatic, relapsed, refractory
- Medical subject headings
- Melanoma, Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tvs-CTL VaccineBiological
autologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL)
| Study group | Role | What they receive |
|---|---|---|
| tvs-CTL Vaccine | Experimental | Infusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells. Receives: Biological: tvs-CTL Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
Measured: 4 weeks
PCR measurement of retroviral construct to measure persistence of infused T-cells
To evaluate how long the infused T-cells remain in the blood stream
Measured: 4 weeks
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
Measured: 4 weeks
Secondary outcomes (3)
PCR measurement of retroviral construct to measure the expansion of infused T-cells
To determine the expansion of infused tvs-CTL in response to repeat vaccination with previously administered vaccines
Measured: 12 months
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
To compare the frequency of tvs-CTL in the peripheral blood, after revaccination, to the frequency noted in the prior study of autologous activated, CAR-transduced T-cells infused in patients with relapsed, refractory Stage IV melanoma
Measured: 12 months
Imaging studies to measure tumor response
Evaluate tumor response to infusion of tvs-CTL and repeat vaccination post-infusion.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2015 (estimated)
- Study start6 Oct 2016
- Primary completion10 Oct 2019
- Study completion13 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary Doolittle
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gary Doolittle, University of Kansas Medical Center
- Investigators
- Gary Doolittle, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02482532
- Sponsor's protocol ID
- Mel-2012-01-01
- Acronym
- MARVSmALo
- Status last verified
- Nov 2021
- First submitted
- 18 Jun 2015
- Last updated
- 4 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Vaccine Enriched, Autologous, Activated T-Cells Redirected to the Tumor Marker GD2 in Patients With Relapsed/Refractory Melanoma
- ClinicalTrials.gov ID
- NCT02482532
- Acronym / sponsor ID
- MARVSmALo / Mel-2012-01-01
- Conditions
- Melanoma
- Keywords
- Melanoma, metastatic, relapsed, refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Gary DoolittleUniversity, hospital or other
- Study start
- 6 Oct 2016 (actual)
- Primary completion
- 10 Oct 2019 (actual)
- Study completion
- 13 Sep 2021 (actual)
- First posted
- 26 Jun 2015 (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.
The researchers will investigate if modified T-cells from a patients own system can be utilized to find and destroy metastatic melanoma tumor and thus improve patient outcomes.
Detailed description
The rate of progression free survival at one (1) year is < 20% for patients with stage IV metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for achieving prolonged survival or even cure, therefore,efforts have focused on several different approaches. Such approaches have used tumor vaccination, adoptive transfer of tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated to cytokines, toxins, or radionucleotides.
The tumor-associated antigen GD2 has been noted on the surface of several tumors, most notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous, T-cells in patients with neuroblastoma. It is the investigators intention to enrich peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well understood vaccines. The investigators will then modify the T-cells to attack the GD2 antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused into the patient following revaccination with the common vaccines. The Investigators will monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR) assays following vaccination.
The Investigators then intend to re-vaccinate with the selected vaccines one month following infusion and monitor for expansion of the modified T-cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tvs-CTL Vaccine | Experimental | Biological: tvs-CTL VaccineInfusion of activated T-cells generated from a patient's own peripheral blood mononuclear cells. |
Who may qualify
- Ages
- 18 to 66 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any stage, where the patient is unable to receive or complete standard therapy
- Life expectancy of at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
- Laboratory Values
- Pulse oximetry of > 95% on room air.
Key exclusion criteria (16 listed)
- Patients with rapidly progressive disease.
- Patient is currently receiving any investigational drugs
- Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph, pulmonary metastatic lesions are allowed
- Patients must not have tumor in a location where enlargement could cause airway obstruction
- Patient is pregnant or lactating
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 |
|---|---|---|
| tvs-CTL Vaccineautologous, 14g2a.zeta chimeric receptor transduced, activated T-cells, enriched for vaccine specific cytotoxic T-lymphocytes (tvs-CTL) | Biological | tvs-CTL Vaccine |
Primary outcome
Measurement of infusion related adverse events to evaluate the safety of infused T-cells
Time frame: 4 weeks
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
PCR measurement of retroviral construct to measure persistence of infused T-cells
Time frame: 4 weeks
To evaluate how long the infused T-cells remain in the blood stream
Measurement of replication competent retrovirus to evaluate the safety of infused T-cells
Time frame: 4 weeks
To evaluate the safety of autologous, receptor-transduced, activated T-cells, enriched for vaccine-specific cytotoxic T-lymphocytes (tvs-CTL)
3 secondary outcomes
PCR measurement of retroviral construct to measure the expansion of infused T-cells
Time frame: 12 months
PCR measurement of retroviral construct to compare frequency of peripheral tvs-CTL population pre-infusion vs post-revaccination
Time frame: 12 months
Imaging studies to measure tumor response
Time frame: 10 weeks
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 4 Feb 2022.
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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.
Gary Doolittle, MD principal investigator
University of Kansas Medical Center
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 tvs-CTL Vaccine in people with Melanoma, run by Gary Doolittle 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 11 inclusion and 16 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 4 Feb 2022. 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?
Measurement of infusion related adverse events to evaluate the safety of infused T-cells (time frame: 4 weeks). The study lists 3 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 4 Feb 2022.