Metastatic MelanomaPhase 1/2NCT01369888
Use of IL-15 After Chemotherapy and Lymphocyte Transfer in Metastatic Melanoma
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Tumor Infiltrating Lymphocytes in people with Metastatic Melanoma and Skin Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Read more about this study
- Who is it for?
- Ages 18 to 66 years
- Conditions the study is for
- Metastatic Melanoma, Skin Cancer
- What is being tested?
- Cyclophosphamide, Fludarabine and Tumor Infiltrating Lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to May 2014
- Phase
- Phase 1/2
- 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 to 66 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Measurable metastatic melanoma with available autologous tumor infiltrating lymphocyte (TIL).
- Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
- Greater than or equal to 18 years of age and less than or equal to age 66.
- Able to understand and sign the Informed Consent Document
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Life expectancy of greater than three months.
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- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- Serology:
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- Hematology:
- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
- White blood cell (WBC) (> 3000/mm^3).
- Platelet count greater than 100,000/mm^3.
- Hemoglobin greater than 8.0 g/dl.
- Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dl.
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
- Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
- Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy, at the time the patient receives the preparative regimen to allow antibody levels to decline.
- Patients who have previously received any anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
Who cannot join
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent systemic steroid therapy.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
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- Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
- In patients > 60 years old, documented LVEF of less than or equal to 45%.
- Documented LVEF of less than or equal to 45% tested in patients with:
- clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or.
- age greater than or equal to 60 years old.
- Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
- Symptoms of respiratory dysfunction.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I/II Study of IL-15 Administration Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen and Autologous Lymphocyte Transfer in Metastatic Melanoma
Background:
- Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body.
Read more
Objectives:
-To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma.
Eligibility:
- Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.
- They will have heart and lung function tests, lab tests, and imaging procedures.
- Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.
- Patients may not be pregnant or nursing.
Read the detailed description
Background:
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- In our analysis of factors that relate to the ability of this treatment to mediate objective responses, we have found a highly significant inverse correlation between reconstitution of cluster of differentiation 4 (CD4)+ forkhead box P3 (Foxp3) + T regulatory cells and the likelihood of achieving an objective response.
- Interleukin 2 (IL-2) administration has been shown to increase the number of T regulatory cells and in our trials we have found a direct relationship between the number of IL-2 doses and the reconstitution of patients at one week with CD4+ Foxp3 + T regulatory cells.
- Interleukin 15 (IL-15) is a strong T cell growth factor, but unlike IL-2, IL-15 is not involved in the generation and maintenance of CD4+ Foxp3 + T regulatory cells that can inhibit immune reactions.
- In pre-clinical adoptive cell transfer studies utilizing a murine melanoma model, the administration of IL-15 following adoptive cell transfer improved anti-tumor effects.
Objectives:
- The primary objective of this trial is to determine the safety, toxicity, and maximum tolerated dose of intravenous recombinant IL-15 administered as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of tumor infiltrating lymphocytes.
- An additional primary objective is to determine whether this combination is able to produce a modest number of clinical responses.
- The secondary objective involves the determination of the level of reconstitution of T regulatory cells in patients who receive cell transfer followed by IL-15 and to determine the pharmacokinetics of IL-15 levels in the serum following intravenous administration.
Eligibility:
- Patients greater than or equal to 18 years old with pathologically confirmed diagnosis of metastatic melanoma.
- Patients with measurable disease, absolute neutrophil count greater than 1000/mm^3 and platelet count greater than 100,000/mm^3.
- No serious comorbid conditions such as active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory or immune systems.
Design:
- Patients with metastatic melanoma will undergo resection to obtain tumor for generation of autologous TIL cultures.
- Patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of autologous Young TIL. In the phase 1 portion of this study, patients will receive recombinant human IL-15 at doses of 0.25, 0.5, 1 or 2 micrograms per kilogram give intravenously daily for 10 days starting on the day of cell transfer. One patient will be treated at the first dose level, if this patient experiences a dose limiting toxicity (DLT), additional patients will be treated at the dose to confirm that no greater than 1/6 patients have DLT prior to proceeding to the next higher level. If 2 DLTs are encountered in this cohort, the study will be terminated. In all other cohorts, groups of three to six patients will receive recombinant human IL-15. Should a single patient experience a dose limiting toxicity due to the cell transfer at a particular dose level, additional patients will be treated at the dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the phase 2 portion. In the phase 2 portion of this study, patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of autologous Young TIL and IL-15 at the maximum tolerated dose (MTD) established in the phase 1 portion.
- Studies will be performed to determine the reconstitution of patients with T regulatory cells and to determine the pharmacokinetics of IL-15 concentration in serum.
- Conditions
- Metastatic Melanoma, Skin Cancer
- Being tested
- Cyclophosphamide, Fludarabine, Tumor Infiltrating Lymphocytes, IL-15
- Keywords
- Immunotherapy, Cell Therapy, IL-15 Cytokine, Melanoma, Metastatic Melanoma, Skin Cancer
- Medical subject headings
- Melanoma, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan
60 mg/m^2, intravenous (IV) (in the vein) x 2 days
FludarabineDrug
Also called Fludara
25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating LymphocytesBiological
Also called TIL
IV over 30 minutes on day 0
IL-15Drug
Also called Interleukin 15
IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
| Study group | Role | What they receive |
|---|---|---|
| IL-15 following Young TIL (0.25 mcg) | Experimental | 0.25 mcg/kg/day x 10 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor Infiltrating Lymphocytes; Drug: IL-15 |
| IL-15 following Young TIL (0.50 mcg) | Experimental | 0.50 mcg/kg/day x 10 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor Infiltrating Lymphocytes; Drug: IL-15 |
| IL-15 Following Young TIL (1 mcg) | Experimental | 1 mcg/kg/day x 10 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor Infiltrating Lymphocytes; Drug: IL-15 |
| IL-15 Following Young TIL (2 mcg) | Experimental | 2 mcg/kg/day x 10 Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor Infiltrating Lymphocytes; Drug: IL-15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Measured: 2 years
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: 8 months, 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2014
- Study completionMay 2014
Why it stopped: Closed this protocol due to autoimmune toxicity.
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Steven A Rosenberg, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01369888
- Sponsor's protocol ID
- 110170
- Other IDs
- 11-C-0170
- Status last verified
- Jan 2015
- First submitted
- 8 Jun 2011
- Last updated
- 27 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
PubMed 17237035Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. doi: 10.1200/JCO.1999.17.7.2105.
PubMed 10561265Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.
PubMed 17200963
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of IL-15 Administration Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen and Autologous Lymphocyte Transfer in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01369888
- Acronym / sponsor ID
- 110170
- Conditions
- Metastatic Melanoma, Skin Cancer
- Keywords
- Immunotherapy, Cell Therapy, IL-15 Cytokine, Melanoma, Metastatic Melanoma, Skin Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed this protocol due to autoimmune toxicity.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 9 Jun 2011 (estimated)
- Results
- Posted 27 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body.
Objectives:
-To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma.
Eligibility:
- Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.
- They will have heart and lung function tests, lab tests, and imaging procedures.
- Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.
- Patients may not be pregnant or nursing.
Detailed description
Background:
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- In our analysis of factors that relate to the ability of this treatment to mediate objective responses, we have found a highly significant inverse correlation between reconstitution of cluster of differentiation 4 (CD4)+ forkhead box P3 (Foxp3) + T regulatory cells and the likelihood of achieving an objective response.
- Interleukin 2 (IL-2) administration has been shown to increase the number of T regulatory cells and in our trials we have found a direct relationship between the number of IL-2 doses and the reconstitution of patients at one week with CD4+ Foxp3 + T regulatory cells.
- Interleukin 15 (IL-15) is a strong T cell growth factor, but unlike IL-2, IL-15 is not involved in the generation and maintenance of CD4+ Foxp3 + T regulatory cells that can inhibit immune reactions.
- In pre-clinical adoptive cell transfer studies utilizing a murine melanoma model, the administration of IL-15 following adoptive cell transfer improved anti-tumor effects.
Objectives:
- The primary objective of this trial is to determine the safety, toxicity, and maximum tolerated dose of intravenous recombinant IL-15 administered as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of tumor infiltrating lymphocytes.
- An additional primary objective is to determine whether this combination is able to produce a modest number of clinical responses.
- The secondary objective involves the determination of the level of reconstitution of T regulatory cells in patients who receive cell transfer followed by IL-15 and to determine the pharmacokinetics of IL-15 levels in the serum following intravenous administration.
Eligibility:
- Patients greater than or equal to 18 years old with pathologically confirmed diagnosis of metastatic melanoma.
- Patients with measurable disease, absolute neutrophil count greater than 1000/mm^3 and platelet count greater than 100,000/mm^3.
- No serious comorbid conditions such as active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory or immune systems.
Design:
- Patients with metastatic melanoma will undergo resection to obtain tumor for generation of autologous TIL cultures.
- Patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of autologous Young TIL. In the phase 1 portion of this study, patients will receive recombinant human IL-15 at doses of 0.25, 0.5, 1 or 2 micrograms per kilogram give intravenously daily for 10 days starting on the day of cell transfer. One patient will be treated at the first dose level, if this patient experiences a dose limiting toxicity (DLT), additional patients will be treated at the dose to confirm that no greater than 1/6 patients have DLT prior to proceeding to the next higher level. If 2 DLTs are encountered in this cohort, the study will be terminated. In all other cohorts, groups of three to six patients will receive recombinant human IL-15. Should a single patient experience a dose limiting toxicity due to the cell transfer at a particular dose level, additional patients will be treated at the dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the phase 2 portion. In the phase 2 portion of this study, patients will receive a non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of autologous Young TIL and IL-15 at the maximum tolerated dose (MTD) established in the phase 1 portion.
- Studies will be performed to determine the reconstitution of patients with T regulatory cells and to determine the pharmacokinetics of IL-15 concentration in serum.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IL-15 following Young TIL (0.25 mcg) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor Infiltrating Lymphocytes, Drug: IL-150.25 mcg/kg/day x 10 |
| IL-15 following Young TIL (0.50 mcg) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor Infiltrating Lymphocytes, Drug: IL-150.50 mcg/kg/day x 10 |
| IL-15 Following Young TIL (1 mcg) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor Infiltrating Lymphocytes, Drug: IL-151 mcg/kg/day x 10 |
| IL-15 Following Young TIL (2 mcg) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor Infiltrating Lymphocytes, Drug: IL-152 mcg/kg/day x 10 |
Who may qualify
- Ages
- 18 to 66 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria.
Key exclusion criteria (14 listed)
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent systemic steroid therapy.
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 |
|---|---|---|
| CyclophosphamideAlso: Cytoxan60 mg/m^2, intravenous (IV) (in the vein) x 2 days | Drug | IL-15 Following Young TIL (1 mcg), IL-15 Following Young TIL (2 mcg), IL-15 following Young TIL (0.25 mcg), IL-15 following Young TIL (0.50 mcg) |
| FludarabineAlso: Fludara25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1) | Drug | IL-15 Following Young TIL (1 mcg), IL-15 Following Young TIL (2 mcg), IL-15 following Young TIL (0.25 mcg), IL-15 following Young TIL (0.50 mcg) |
| Tumor Infiltrating LymphocytesAlso: TILIV over 30 minutes on day 0 | Biological | IL-15 Following Young TIL (1 mcg), IL-15 Following Young TIL (2 mcg), IL-15 following Young TIL (0.25 mcg), IL-15 following Young TIL (0.50 mcg) |
| IL-15Also: Interleukin 15IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients. | Drug | IL-15 Following Young TIL (1 mcg), IL-15 Following Young TIL (2 mcg), IL-15 following Young TIL (0.25 mcg), IL-15 following Young TIL (0.50 mcg) |
Primary outcome
Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
Time frame: 2 years
Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Number of Participants With Adverse Events
Time frame: 8 months, 9 days
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17237035Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
- Background: PubMed 10561265Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. doi: 10.1200/JCO.1999.17.7.2105.
- Background: PubMed 17200963Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.
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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, M.D. principal investigator
National Cancer Institute (NCI)
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 Cyclophosphamide, Fludarabine and Tumor Infiltrating Lymphocytes in people with Metastatic Melanoma and Skin Cancer, run by National Cancer Institute (NCI) 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 24 inclusion and 14 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: stopped early, as of the sponsor's last update on 27 Jan 2015. 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 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?
Yes. Results are posted in the registry (first posted 27 Jan 2015). 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?
Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL. (time frame: 2 years). 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 NCT01369888, which also lists 3 linked publications.
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 27 Jan 2015.