Melanoma (Skin)Phase 1/2NCT00056134
Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
A Phase 1/2 study testing Dendritic cell vaccine plus denileukin difitox in people with Melanoma (Skin), run by University Hospital Erlangen at 1 site in Germany.
Trial summary
RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- Dendritic cell vaccine plus denileukin difitox
- Type of treatment
- Vaccines
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2002to May 2012
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed locoregional or metastatic cutaneous malignant melanoma
- Stage III or IV disease
- Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
- Stage IV: any pT, N1-2, M1a-b
- Surgically incurable
- Incurable with standard treatment (i.e., localized chemotherapy/limb perfusion for stage III, systemic chemotherapy for stage IV)
- Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III lesions may be measurable lymph nodes after incomplete resection and/or inoperable in transit metastases
- HLA-A1 and/or HLA-A2 expression by serologic HLA typing
- HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells
- No active CNS metastases
- Previously treated CNS metastases (e.g., excision of a single metastasis) allowed if no active disease present by CT scan or MRI
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- Karnofsky 60-100%
Life expectancy
- At least 6 months
Hematopoietic
- WBC greater than 2,500/mm^3
- Neutrophil count greater than 1,000/mm^3
- Lymphocyte count greater than 700/mm^3
- Platelet count greater than 75,000/mm^3
- Hemoglobin greater than 9 g/dL
- No bleeding disorders
Hepatic
- Bilirubin less than 2.0 mg/dL
- No hepatitis B or C
Renal
- Creatinine less than 2.5 mg/dL
Cardiovascular
- No clinically significant heart disease
Pulmonary
- No clinically significant respiratory disease
Immunologic
- No active systemic infection
- No immunodeficiency disease
- No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1
- No active autoimmune disease including, but not limited to:
- Lupus erythematosus
- Autoimmune thyroiditis or uveitis
- Multiple sclerosis
- Inflammatory bowel disease NOTE: Vitiligo allowed
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after study participation
- No organic brain syndrome or significant psychiatric abnormality that would preclude study participation and follow-up
- No contraindication to leukapheresis
- No other active malignant neoplasms
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior systemic immunotherapy
- No concurrent immunotherapy during and for 2 weeks after last vaccination
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
- No concurrent chemotherapy during and for 2 weeks after last vaccination
Endocrine therapy
- No concurrent corticosteroids during and for 2 weeks after last vaccination
Radiotherapy
- No prior radiotherapy to the spleen
- Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or local complications such as compression)
Surgery
- See Disease Characteristics
- Recovered from prior surgery
- No prior splenectomy
- No prior organ allografts
- Concurrent surgery of selected metastases (e.g., pain or local complications such as compression) allowed
Other
- No other concurrent investigational drugs during and for 2 weeks after last vaccination
- No concurrent paramedical substance during and for 2 weeks after last vaccination
- No concurrent participation or intent to participate in another clinical trial
Trial locations and contacts
1 site in 1 country.
Germany1 site
Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
Erlangen, D-91052
About this study
Official title: Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma.
Read the detailed description
OBJECTIVES:
- Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or HLA-A2.1-positive stage III or IV melanoma.
- Determine the safety and tolerability of these vaccinations in these patients.
- Determine tumor response in patients treated with these vaccinations.
OUTLINE:
- Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC are processed for the generation of dendritic cells (DC) to be used for vaccinations. DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.
Patients who show a tumor response (at least stable disease) may receive vaccination #5 and further booster vaccinations.
- Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6 additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692 in the absence of disease progession or unacceptable toxicity.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.
- Conditions
- Melanoma (Skin)
- Being tested
- Dendritic cell vaccine plus denileukin difitox
- Keywords
- recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic cell vaccine plus denileukin difitoxBiological
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by clinical and laboratory evaluation at every visit
Overall survival as assessed by clinical staging (CT scan and positron emission tomography [PET]) every 3 months
Secondary outcomes (4)
Depletion of regulatory T-cells as assessed by tetramer stainings at every visit
Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit
Time to progression as assessed by clinical staging (CT scan and PET) every 3 months
Objective response rate as assessed by clinical staging (CT scan and PET) every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2003 (estimated)
- Study startOct 2002
- Primary completionOct 2011
- Study completionMay 2012
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Erlangen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, PD Dr. med. univ. Beatrice Schuler-Thurner, University Hospital Erlangen
- Investigators
- Gerold Schuler, Study chair, Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00056134
- Sponsor's protocol ID
- CDR0000270762
- Other IDs
- ERLANGEN-ONTAK, EU-20246
- Status last verified
- Feb 2018
- First submitted
- 6 Mar 2003
- Last updated
- 19 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Baur AS, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kampgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G. Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood. 2013 Sep 26;122(13):2185-94. doi: 10.1182/blood-2012-09-456988. Epub 2013 Aug 19.
PubMed 23958949
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccination of HLA-A1 and/or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide-Loaded Autologous Dendritic Cells With Prior Depletion of CD25-Positive Cells Using Denileukin Difitox (ONTAK)
- ClinicalTrials.gov ID
- NCT00056134
- Acronym / sponsor ID
- CDR0000270762
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University Hospital ErlangenUniversity, hospital or other
- Study start
- Oct 2002
- Primary completion
- Oct 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 7 Mar 2003 (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: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma.
Detailed description
OBJECTIVES:
- Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or HLA-A2.1-positive stage III or IV melanoma.
- Determine the safety and tolerability of these vaccinations in these patients.
- Determine tumor response in patients treated with these vaccinations.
OUTLINE:
- Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC are processed for the generation of dendritic cells (DC) to be used for vaccinations. DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.
Patients who show a tumor response (at least stable disease) may receive vaccination #5 and further booster vaccinations.
- Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6 additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692 in the absence of disease progession or unacceptable toxicity.
Patients are followed for 10 years.
PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 120 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 |
|---|---|---|
| Dendritic cell vaccine plus denileukin difitox | Biological | – |
Primary outcome
Safety and tolerability as assessed by clinical and laboratory evaluation at every visit
Overall survival as assessed by clinical staging (CT scan and positron emission tomography [PET]) every 3 months
4 secondary outcomes
Depletion of regulatory T-cells as assessed by tetramer stainings at every visit
Induction of antigen-specific immune responses as assessed by elispot and tetramer staining at every visit
Time to progression as assessed by clinical staging (CT scan and PET) every 3 months
Objective response rate as assessed by clinical staging (CT scan and PET) every 3 months
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 19 Feb 2018.
- Derived from this study: PubMed 23958949Baur AS, Lutz MB, Schierer S, Beltrame L, Theiner G, Zinser E, Ostalecki C, Heidkamp G, Haendle I, Erdmann M, Wiesinger M, Leisgang W, Gross S, Pommer AJ, Kampgen E, Dudziak D, Steinkasserer A, Cavalieri D, Schuler-Thurner B, Schuler G. Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood. 2013 Sep 26;122(13):2185-94. doi: 10.1182/blood-2012-09-456988. Epub 2013 Aug 19.
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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.
Gerold Schuler study chair
Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
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 Dendritic cell vaccine plus denileukin difitox in people with Melanoma (Skin), run by University Hospital Erlangen at 1 site in Germany.
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 19 Feb 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 Germany. 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?
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?
Safety and tolerability as assessed by clinical and laboratory evaluation at every visit. 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?
On the ClinicalTrials.gov record for NCT00056134, 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 19 Feb 2018.