Melanoma (Skin)Phase 1NCT00324623
Cyclophosphamide and Fludarabine Followed by Cellular Adoptive Immunotherapy and Vaccine Therapy in Patients With Metastatic Melanoma
A Phase 1 study testing Melan-A VLP vaccine, IMP321 adjuvant, adoptive immunotherapy and therapeutic autologous lymphocytes in people with Melanoma (Skin), run by Prof. Serge Leyvraz at 1 site in Switzerland.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, may be used to prepare the body for other treatments, such as cellular adoptive immunotherapy. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- Melan-A VLP vaccine, IMP321 adjuvant, adoptive immunotherapy and therapeutic autologous lymphocytes
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteSwitzerland
- Study dates
- Sep 2005to Nov 2011
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of metastatic melanoma
- Progressive disease after receiving prior Melan-A peptide vaccine on an immunotherapy protocol of the Ludwig Institute AND achieved a detectable immune response (increase of specific CD8^+ TET^+ Melan-A)
- Tumor must express MART-1/Melan-A antigen
- HLA-A2 positive
- Not eligible for other protocols due to progressive disease OR maximum number of vaccine injections with stable disease has been attained
PATIENT CHARACTERISTICS:
- Performance status 0-2
- Whole blood counts normal
- Pulmonary status normal
- Transaminases < 1.5 times upper limit of normal (ULN)
- Gamma-glutamyl-transferase < 1.5 times ULN
- Bilirubin normal
- Creatinine clearance > 70 mL/min
- No major uncontrolled heart disease
- No arterial hypertension
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior chemotherapy, biologic therapy, radiotherapy, and/or surgery allowed
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
About this study
Official title: Phase I Study of In Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, may be used to prepare the body for other treatments, such as cellular adoptive immunotherapy. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. Giving cyclophosphamide together with fludarabine followed by biological therapy may be an effective treatment for metastatic melanoma.
PURPOSE: This phase I trial is studying the side effects of giving cyclophosphamide together with fludarabine followed by cellular adoptive immunotherapy, and vaccine therapy in treating patients with metastatic melanoma.
Read the detailed description
OBJECTIVES:
- Determine the magnitude and duration of the expansion of antigen-specific T-cells present in post-vaccination peripheral blood mononuclear cells and reinfused after immunosuppression in patients with metastatic melanoma.
- Characterize the T-cell subsets (phenotype, function, T-cell receptor repertoire) in these patients.
- Determine the tumor response in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is an open-label dose-finding study. Patients undergo leukapheresis to collect whole peripheral blood mononuclear cells (PBMC). Patients are then assigned to 1 of 3 treatment groups.
- Group 1 (closed to accrual as of 5/8/2007): Patients receive cyclophosphamide IV on days -7 and -6 and fludarabine IV on days -5 to -3. Patients undergo autologous PBMC infusion on day 0. Patients also receive vaccination comprising Melan-A vaccine emulsified in incomplete Freund's adjuvant (IFA) subcutaneously (SC) once every 3 weeks beginning on day 0.
- Group 2 (closed to accrual as of 8/15/2007): Patients receive cyclophosphamide IV at a higher dose than in group 1 on days -7 and -6 and fludarabine IV on days -5 to -3. Patients also receive an autologous PBMC infusion and Melan-A vaccine emulsified in IFA as in group 1.
- Group 3: Patients receive cyclophosphamide IV at 30 mg/kg on days -7 and -6. Patients also receive fludarabine 30 mg/m2 IV on days -5 to -3, autologous PBMC infusion on day 0,and Melan-A vaccine emulsified in IFA and IMP321. The first 3 patients receive 25 micrograms of IMP321, in the absence of severe 3 or 4 toxicity, the dose will be escalated to IMP321 250 micrograms.
PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.
- Conditions
- Melanoma (Skin)
- Being tested
- Melan-A VLP vaccine, IMP321 adjuvant, adoptive immunotherapy, therapeutic autologous lymphocytes, cyclophosphamide, fludarabine phosphate
- Keywords
- stage IV melanoma, recurrent melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melan-A VLP vaccine, IMP321 adjuvantBiological
adoptive immunotherapyBiological
therapeutic autologous lymphocytesBiological
cyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| Lymphodepletion, vaccine, IMP321 adjuvant | Experimental | Not described Receives: Biological: Melan-A VLP vaccine, IMP321 adjuvant; Biological: adoptive immunotherapy; Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phenotype, function, and T-cell receptor repertoire
Measured: Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine
Tumor response
Measured: Tumor response evaluated 4 weeks after last vaccine
Toxicity
Measured: Within 30 days after completion of the last vaccine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startSep 2005
- Primary completionNov 2011
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.
- 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Serge Leyvraz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Serge Leyvraz, Centre Hospitalier Universitaire Vaudois
- Investigators
- Serge Leyvraz, MD, Study chair, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00324623
- Sponsor's protocol ID
- CDR0000468827
- Other IDs
- CHUV-CEPO-ITA-02, EU-20607
- Status last verified
- Nov 2012
- First submitted
- 10 May 2006
- Last updated
- 20 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Romano E, Michielin O, Voelter V, Laurent J, Bichat H, Stravodimou A, Romero P, Speiser DE, Triebel F, Leyvraz S, Harari A. MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial. J Transl Med. 2014 Apr 12;12:97. doi: 10.1186/1479-5876-12-97.
PubMed 24726012
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of In Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT00324623
- Acronym / sponsor ID
- CDR0000468827
- Conditions
- Melanoma (Skin)
- Keywords
- stage IV melanoma, recurrent melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Prof. Serge LeyvrazUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Nov 2011 (actual)
- First posted
- 11 May 2006 (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: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, may be used to prepare the body for other treatments, such as cellular adoptive immunotherapy. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. Giving cyclophosphamide together with fludarabine followed by biological therapy may be an effective treatment for metastatic melanoma.
PURPOSE: This phase I trial is studying the side effects of giving cyclophosphamide together with fludarabine followed by cellular adoptive immunotherapy, and vaccine therapy in treating patients with metastatic melanoma.
Detailed description
OBJECTIVES:
- Determine the magnitude and duration of the expansion of antigen-specific T-cells present in post-vaccination peripheral blood mononuclear cells and reinfused after immunosuppression in patients with metastatic melanoma.
- Characterize the T-cell subsets (phenotype, function, T-cell receptor repertoire) in these patients.
- Determine the tumor response in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is an open-label dose-finding study. Patients undergo leukapheresis to collect whole peripheral blood mononuclear cells (PBMC). Patients are then assigned to 1 of 3 treatment groups.
- Group 1 (closed to accrual as of 5/8/2007): Patients receive cyclophosphamide IV on days -7 and -6 and fludarabine IV on days -5 to -3. Patients undergo autologous PBMC infusion on day 0. Patients also receive vaccination comprising Melan-A vaccine emulsified in incomplete Freund's adjuvant (IFA) subcutaneously (SC) once every 3 weeks beginning on day 0.
- Group 2 (closed to accrual as of 8/15/2007): Patients receive cyclophosphamide IV at a higher dose than in group 1 on days -7 and -6 and fludarabine IV on days -5 to -3. Patients also receive an autologous PBMC infusion and Melan-A vaccine emulsified in IFA as in group 1.
- Group 3: Patients receive cyclophosphamide IV at 30 mg/kg on days -7 and -6. Patients also receive fludarabine 30 mg/m2 IV on days -5 to -3, autologous PBMC infusion on day 0,and Melan-A vaccine emulsified in IFA and IMP321. The first 3 patients receive 25 micrograms of IMP321, in the absence of severe 3 or 4 toxicity, the dose will be escalated to IMP321 250 micrograms.
PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lymphodepletion, vaccine, IMP321 adjuvant | Experimental | Biological: Melan-A VLP vaccine, IMP321 adjuvant, Biological: adoptive immunotherapy, Biological: therapeutic autologous lymphocytes, Drug: cyclophosphamide, Drug: fludarabine phosphate |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Melan-A VLP vaccine, IMP321 adjuvant | Biological | Lymphodepletion, vaccine, IMP321 adjuvant |
| adoptive immunotherapy | Biological | Lymphodepletion, vaccine, IMP321 adjuvant |
| therapeutic autologous lymphocytes | Biological | Lymphodepletion, vaccine, IMP321 adjuvant |
| cyclophosphamide | Drug | Lymphodepletion, vaccine, IMP321 adjuvant |
| fludarabine phosphate | Drug | Lymphodepletion, vaccine, IMP321 adjuvant |
Primary outcome
Phenotype, function, and T-cell receptor repertoire
Time frame: Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine
Tumor response
Time frame: Tumor response evaluated 4 weeks after last vaccine
Toxicity
Time frame: Within 30 days after completion of the last vaccine
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 20 Nov 2012.
- Derived from this study: PubMed 24726012Romano E, Michielin O, Voelter V, Laurent J, Bichat H, Stravodimou A, Romero P, Speiser DE, Triebel F, Leyvraz S, Harari A. MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial. J Transl Med. 2014 Apr 12;12:97. doi: 10.1186/1479-5876-12-97.
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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.
Serge Leyvraz, MD study chair
Centre Hospitalier Universitaire Vaudois
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 Melan-A VLP vaccine, IMP321 adjuvant, adoptive immunotherapy and therapeutic autologous lymphocytes in people with Melanoma (Skin), run by Prof. Serge Leyvraz at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 20 Nov 2012. 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 Switzerland. 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?
Phenotype, function, and T-cell receptor repertoire (time frame: Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine). 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?
On the ClinicalTrials.gov record for NCT00324623, 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 20 Nov 2012.