Melanoma (Skin)Phase 2NCT00863330
Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma
A Phase 2 study testing Tumor Infiltrating Lymphocytes (TIL) in people with Melanoma (Skin), run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes 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?
- Tumor Infiltrating Lymphocytes (TIL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Jul 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 metastatic melanoma
- Refractory to standard treatment including high-dose aldesleukin (IL-2), unless previously ineligible for or refused IL-2
- Measurable disease with ≥ 1 lesion that is resectable for tumor-infiltrating lymphocyte generation
- Patients with ≥ 1 brain metastases < 1 cm each, or 1-2 brain metastases > 1 cm are eligible provided they have been treated and stable for ≥ 3 months
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy > 3 months
- ANC > 1,000/mm^3 (without filgrastim support)
- WBC > 3,000/mm^3
- Hemoglobin > 8.0 g/dL
- Platelet count > 100,000/mm^3
- Serum ALT/AST < 3 times upper limit of normal
- Total bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)
- Serum creatinine ≤ 1.6 mg/dL
- LVEF > 45% in patients meeting the following criteria:
- Clinically significant atrial and/or ventricular arrhythmias, including, but not limited to, atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block
- At least 60 years of age
- FEV_1 > 60% in patients meeting the following criteria:
- Prolonged history of cigarette smoking
- Symptoms of respiratory dysfunction
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 months after completion of study treatment
- No HIV or hepatitis B or C positivity
- No form of primary immunodeficiency (e.g., severe combined immunodeficiency disease or AIDS)
- No opportunistic infections
- No active systemic infections
- No history of severe immediate hypersensitivity reaction to any of the agents used in this study
- No coagulation disorders
- No myocardial infarction, cardiac arrhythmias, or positive stress thallium or comparable test
- No history of coronary revascularization or ischemic symptoms
- No obstructive or restrictive pulmonary disease
- No other active major medical illness of the cardiovascular, respiratory, or immune system
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy (alopecia or vitiligo allowed)
- At least 6 weeks since prior ipilimumab
- Must have normal colonoscopy with normal colonic biopsies
- At least 4 weeks since prior systemic therapy
- Minor surgical procedures within the past 3 weeks allowed provided all toxicities have recovered to ≤ grade 1
- No concurrent systemic steroids
- No other concurrent experimental agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
About this study
Official title: A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated lymphocytes and aldesleukin together with cyclophosphamide and fludarabine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma.
- Determine the toxicity of this treatment regimen.
Secondary
- Determine the rate of repopulation of the young TIL cells.
- Establish in vitro immunological correlates that predict in vivo persistence and clinical response.
OUTLINE:
- Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
- Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.
Patients with stable disease, partial response, or recurrent disease after initial response may receive 1 additional course of treatment (as above) beginning 8 weeks after completion of aldesleukin.
Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then periodically thereafter for research studies. Samples are analyzed for differences in function and phenotype prior to and after TIL infusion. The immunological correlates of treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to determine cell phenotype and function; correlation of in vitro characteristics of the infused cells with in vivo antitumor activity; and the activity, specificity, and telomere length using flow FISH.
After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
- Conditions
- Melanoma (Skin)
- Being tested
- Tumor Infiltrating Lymphocytes (TIL)
- 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.
Tumor Infiltrating Lymphocytes (TIL)Biological
Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
| Study group | Role | What they receive |
|---|---|---|
| Determine toxicity of treatment regimen. | Experimental | Not described Receives: Biological: Tumor Infiltrating Lymphocytes (TIL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Objective
Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.
Measured: 4-6 weeks after completion of TIL
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: administrative decision- PI retired and treating physician left the institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John P. Hanson, MD, Principal investigator, St. Luke's Medical CenterJonathan S. Treisman, MD, Principal investigator, St. Luke's Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00863330
- Sponsor's protocol ID
- CDR0000636885
- Other IDs
- STLMC-L-0839
- Status last verified
- Dec 2014
- First submitted
- 17 Mar 2009
- Last updated
- 3 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00863330
- Acronym / sponsor ID
- CDR0000636885
- Conditions
- Melanoma (Skin)
- Keywords
- stage IV melanoma, recurrent melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: administrative decision- PI retired and treating physician left the institution
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 18 Mar 2009 (estimated)
- Results
- Posted 17 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated lymphocytes and aldesleukin together with cyclophosphamide and fludarabine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma.
Detailed description
OBJECTIVES:
Primary
- Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma.
- Determine the toxicity of this treatment regimen.
Secondary
- Determine the rate of repopulation of the young TIL cells.
- Establish in vitro immunological correlates that predict in vivo persistence and clinical response.
OUTLINE:
- Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
- Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.
Patients with stable disease, partial response, or recurrent disease after initial response may receive 1 additional course of treatment (as above) beginning 8 weeks after completion of aldesleukin.
Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then periodically thereafter for research studies. Samples are analyzed for differences in function and phenotype prior to and after TIL infusion. The immunological correlates of treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to determine cell phenotype and function; correlation of in vitro characteristics of the infused cells with in vivo antitumor activity; and the activity, specificity, and telomere length using flow FISH.
After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Determine toxicity of treatment regimen. | Experimental | Biological: Tumor Infiltrating Lymphocytes (TIL) |
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 |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL)Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2. | Biological | Determine toxicity of treatment regimen. |
Primary outcome
Primary Objective
Time frame: 4-6 weeks after completion of TIL
Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John P. Hanson, MD principal investigator
St. Luke's Medical Center
Jonathan S. Treisman, MD principal investigator
St. Luke's 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 2 study testing Tumor Infiltrating Lymphocytes (TIL) in people with Melanoma (Skin), run by Wake Forest University Health Sciences 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?
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: stopped early, as of the sponsor's last update on 3 Oct 2024. 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 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?
Yes. Results are posted in the registry (first posted 17 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Primary Objective (time frame: 4-6 weeks after completion of TIL). 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 3 Oct 2024.