Melanoma (Skin)Phase 1NCT00085462
Gene-Modified White Blood Cells Followed By Interleukin-2 and Vaccine Therapy in Treating Patients With Metastatic Melanoma
A Phase 1 study testing aldesleukin, filgrastim and gp100-fowlpox vaccine in people with Melanoma (Skin), run by National Institutes of Health Clinical Center (CC) at 2 sites in United States.
Trial summary
RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. 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?
- aldesleukin, filgrastim and gp100-fowlpox vaccine
- Type of treatment
- Vaccines
- How many people
- 61 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2004to Sep 2008
- 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
DISEASE CHARACTERISTICS:
- Diagnosis of melanoma
- Metastatic disease
- Measurable disease
- Refractory to standard therapy, including high-dose interleukin-2 therapy
- HLA-A*0201 positive
- Progressive disease during prior immunization to melanoma antigens OR prior treatment with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) cellular therapy with or without myeloablation allowed provided toxicity resolved to ≤ grade 2 (except vitiligo) AND patient does not require systemic steroids
- No brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- Lymphocyte count > 500/mm^3
- WBC > 3,000/mm^3
- No coagulation disorders
Hepatic
- AST and ALT < 3 times upper limit of normal (ULN)
- Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL in patients with Gilbert's syndrome)
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative (unless antigen negative)
Renal
- Creatinine ≤ 1.6 mg/dL
Cardiovascular
- LVEF ≥ 45% by cardiac stress test
- No LVEF < 45% in patients ≥ 50 years of age
- No myocardial infarction
- No cardiac arrhythmias
- No symptomatic cardiac ischemia
- No prior EKG abnormalities
- No other major cardiovascular illness
Pulmonary
- FEV_1 ≥ 60% of predicted AND no obstructive or restrictive pulmonary disease
- No symptoms of respiratory dysfunction
- No other major respiratory illness
Immunologic
- HIV negative
- Epstein-Barr virus positive
- No active systemic infections (including opportunistic infections)
- No form of primary (e.g., autoimmune colitis or Crohn's disease) or secondary immunodeficiency (due to chemotherapy or radiotherapy)
- No prior severe immediate hypersensitivity reaction to any of the study agents including eggs
- No other major illness of the immune system
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 month after study participation
- Willing to complete a durable power of attorney (DPA)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- More than 6 weeks since prior MDX-010
Chemotherapy
- Not specified
Endocrine therapy
- See Disease Characteristics
- No concurrent systemic steroid therapy
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- More than 4 weeks since other prior systemic therapy and recovered
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
NCI - Surgery Branch
Bethesda, Maryland, 20892-1201
About this study
Official title: Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2.
Secondary
- Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen.
OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no).
Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
- Stratum 2 (CD8+peripheral blood lymphocytes [PBL]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.
Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course.
Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter.
PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.
- Conditions
- Melanoma (Skin)
- Being tested
- aldesleukin, filgrastim, gp100-fowlpox vaccine, therapeutic autologous lymphocytes, therapeutic tumor infiltrating lymphocytes
- Keywords
- recurrent melanoma, stage IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldesleukinBiological
filgrastimBiological
gp100-fowlpox vaccineBiological
therapeutic autologous lymphocytesBiological
therapeutic tumor infiltrating lymphocytesBiological
cyclophosphamideDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study startMay 2004
- Primary completionMay 2007
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Masking
- None (open label)
- Enrolment
- 61 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Steven A. Rosenberg, MD, PhD, Principal investigator, NCI - Surgery Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00085462
- Sponsor's protocol ID
- 040181
- Other IDs
- 04-C-0181, NCI-6470, CDR0000370798
- Status last verified
- Jun 2012
- First submitted
- 10 Jun 2004
- Last updated
- 22 Jun 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
- ClinicalTrials.gov ID
- NCT00085462
- Acronym / sponsor ID
- 040181
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage IV melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (estimated)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2004
- Primary completion
- May 2007 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 11 Jun 2004 (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: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining gene-modified white blood cell infusions with interleukin-2 and vaccine therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying how well giving gene-modified white blood cells when given together with interleukin-2 and vaccine therapy works in treating patients with metastatic melanoma.
Detailed description
OBJECTIVES:
Primary
- Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2.
Secondary
- Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen.
OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no).
Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
- Stratum 2 (CD8+peripheral blood lymphocytes [PBL]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0*.
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover.
Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course.
Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter.
PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- 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 |
|---|---|---|
| aldesleukin | Biological | – |
| filgrastim | Biological | – |
| gp100-fowlpox vaccine | Biological | – |
| therapeutic autologous lymphocytes | Biological | – |
| therapeutic tumor infiltrating lymphocytes | Biological | – |
| cyclophosphamide | Drug | – |
| fludarabine phosphate | Drug | – |
Primary outcome
Not reported in the source record.
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 22 Jun 2012.
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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.
Steven A. Rosenberg, MD, PhD principal investigator
NCI - Surgery Branch
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing aldesleukin, filgrastim and gp100-fowlpox vaccine in people with Melanoma (Skin), run by National Institutes of Health Clinical Center (CC) at 2 sites 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?
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 22 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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 22 Jun 2012.