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Metastatic MelanomaPhase 2NCT01319565

Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI...

A Phase 2 study testing Aldesleukin, Cyclophosphamide and Fludarabine in people with Metastatic Melanoma and Skin Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background: An experimental treatment for metastatic melanoma involves cell therapy, in which researchers take white blood cells (lymphocytes) from the tumor tissue, grow them in the laboratory in large numbers, and then use the cells to attack the tumor tissue. 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?
Aldesleukin, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
1 siteUnited States
Study dates
24 Mar 2011to 10 Sep 2024
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 to 66 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation. The lesion must be of at least 1cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization less than or equal to 7 days).
  • 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 66 years of age.
  • Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
  • Life expectancy of greater than three months
  • Willing to sign a durable power of attorney.
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  • Able to understand and sign the Informed Consent Document
  • Clinical performance status of eastern Cooperative Oncology Group (ECOG) 0 or 1.
  • Hematology:
  • Absolute neutrophil count greater than 1000/mm(3)
  • Hemoglobin greater than 8.0 g/dl
  • Platelet count greater than 100,000/mm(3)
  • 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, or hepatitis C antibody or antigen.
  • Chemistry:
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal.
  • Calculated creatinine clearance (eGFR) > 50 ml/min.
  • Total bilirubin less than or equal to 2 mg/dl, except in patients with
  • Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
  • More than four weeks must have elapsed since any prior systemic therapy at the time of randomization, and patient's toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment.
  • 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 inclusion criteria.
  • Six weeks must have elapsed since any prior anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) antibody therapy to allow antibody levels to decline.
  • Note: Patients who have previously received ipilimumab or tremelimumab, anti-programmed cell death protein 1 (PD1) or anti-programmed cell death ligand 1 (PD-L1) antibodies and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

Who cannot join

  • Prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
  • Women of child-bearing potential who are pregnant or breastfeeding because 10 of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Systemic steroid therapy requirement.
  • Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and acquired immunodeficiency syndrome (AIDS).
  • 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.)
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  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • History of coronary revascularization or ischemic symptoms.
  • Any patient known to have a 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 forced expiratory volume in one second (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
  • Prior radiation therapy that, in the judgment of the radiation oncologist, precludes the administration of total body irradiation.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Short-Term Cultured Tumor-Infiltrating Lymphocytes Plus IL-2 Following Either a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)

Background:

  • An experimental treatment for metastatic melanoma involves cell therapy, in which researchers take white blood cells (lymphocytes) from the tumor tissue, grow them in the laboratory in large numbers, and then use the cells to attack the tumor tissue. Before receiving the cells, chemotherapy is needed to temporarily suppress the immune system to improve the chances that the tumor-fighting cells will be able to survive in the body. In some studies of cell therapy, individuals who have received total body irradiation (TBI) in addition to the chemotherapy (in order to increase the length of time that they do not produce white blood cells) seem to have a slightly better response to the treatment, but it is not known if adding radiation to the cell therapy will cause a better response for all individuals. Researchers are interested in comparing cell therapy given with the usual chemotherapy to cell therapy given with the usual chemotherapy and TBI.
Read more

Objectives:

  • To compare the effectiveness of cell therapy given with chemotherapy to cell therapy given with chemotherapy and total body irradiation in individuals with metastatic melanoma.

Eligibility:

  • Individuals at least 18 years of age who have been diagnosed with metastatic melanoma.

Design:

  • Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
  • Participants will be divided into two groups: cell therapy with chemotherapy alone (group 1) or cell therapy with chemotherapy plus TBI (group 2).
  • All participants will provide a tumor sample from either surgery or a tumor biopsy for white blood cell collection.
  • Participants will have leukapheresis to collect additional white blood cells for cell growth and future testing, and TBI group participants will also provide stem cells to help them recover after radiation. (TBI participants who cannot provide enough stem cells will be moved to the non-radiation treatment group.)
  • Participants will have chemotherapy with cyclophosphamide (two treatments over 2 days) and fludarabine (five treatments over 5 days) starting 7 days before the cell therapy. Participants in the TBI group will also have TBI for the 3 days immediately before the cell therapy.
  • All participants will receive the white blood cells, followed by high dose aldesleukin every 8 hours for up to 5 days after the cell infusion to help keep the therapy cells alive and active. Participants will also have injections of filgrastim to stimulate blood cell production, and participants in the TBI group will also receive their stem cells.
  • Participants will take an antibiotic for at least 6 months after treatment to prevent pneumonia and will be asked to return for regular monitoring and follow-up visits for at least 5 years to evaluate the tumors response to treatment.
Read the detailed description

Background:

  • Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
  • In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria in Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Complete regression rates in these three consecutive trials were 12%, 20%, and 40%, respectively strongly suggesting that the addition of TBI could improve the complete regression rate. Of the 20 complete regressions seen in this trial, 19 are on-going at 37 to 82 months.
  • Because of the complexity of developing selected TIL for use in adoptive transfer, we have recently developed a simplified method for producing TIL that is more applicable to use in outside institutions. Utilizing young TIL cells (sometimes with cluster of differentiation 8 (CD8) purification) in 105 patients, the objective response rate was 34% with a 6.6 % incidence of complete regressions. All patients in this trial received the cyclophosphamide fludarabine regimen alone.
  • Because of the strong suggestion that the addition of TBI to the chemotherapy regimen could increase durable, complete regression rates in patients with metastatic melanoma, we are now attempting to definitively determine whether the addition of TBI to the chemotherapy preparative regimen can improve complete response rates, and overall survival in patients receiving young TIL.

Objectives:

-To determine, in a prospective randomized trial, the complete response rate and survival of patients with metastatic melanoma receiving adoptive cell transfer (ACT) using young TIL plus aldesleukin treatment following either a chemotherapy preparative regimen alone, or the same chemotherapy preparative regimen plus TBI.

Eligibility:

-Patients who are 18 years or older must have:

  • Evaluable metastatic melanoma;
  • Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL;
  • No contraindications to high dose aldesleukin administration or total body irradiation;
  • No concurrent major medical illnesses or any form of immunodeficiency

Design:

-Patients with metastatic melanoma will have lesions resected and after TIL growth is established patients with will be prospectively randomized to receive ACT with young TIL plus aldesleukin following either a non-myeloablative chemotherapy preparative regimen or this same regimen plus TBI.

Being tested
Aldesleukin, Cyclophosphamide, Fludarabine, Young TIL, Total Body Irradiation (TBI)
Keywords
Young TIL, Metastatic Melanoma, Immunotherapy, Adoptive Cell Therapy, 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.

  • AldesleukinDrug

    Also called Interleukin-2

    Arm 1 and Arm 2 - Days 1 to 4: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) for up to 5 days (maximum 15 doses).

  • CyclophosphamideDrug

    Also called Cytoxan

    Arm 1 and Arm 2 - Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 mL dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

  • FludarabineDrug

    Also called Fludara

    Arm 1 and Arm 2 - Days -7 to -3: Fludarabine 25 mg/m^2/day intravenous piggyback (IVPB) daily over 15-30 minutes for 5 days.

  • Young TILBiological

    Also called Young tumor infiltrating lymphocytes

    Arm 1 and Arm 2 - Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.

  • Total Body Irradiation (TBI)Radiation

    Also called TBI

    Arm 2 - Days -3 to -1: Ondansetron 0.15 mg/kg intravenous (IV) x 1 dose pre-total body irradiation (TBI). Patients will then receive 2 Gray (Gy) TBI twice a day for 3 days (total dose 12 Gy using a linear accelerator in Radiation Oncology.

Study groups in NCT01319565
Study groupRoleWhat they receive
Arm 1/Adoptive Cell Therapy (ACT)ExperimentalNon-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin
Receives: Drug: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Young TIL
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)ExperimentalNon-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
Receives: Drug: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Young TIL; Radiation: Total Body Irradiation (TBI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)

    Percentage of participants who have a clinical response to treatment (objective tumor regression) was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as refence the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD.

    Measured: Participants were followed from treatment to progression of disease or until principal investigator (PI) discretion (average 91.8 months).

  2. Overall Survival (OS)

    OS is defined as the time to death following the start of treatment.

    Measured: Participants were followed from treatment until death (median 14 months) or until principal investigator (PI) discretion (median 99.0 months) for participants alive at study closure.

Secondary outcomes (3)

  1. Progression-free Survival (PFS)

    PFS is defined as time to disease progression following the start of treatment. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v3.0. Progressive Disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD. The appearance of one or more new lesions is also considered progression.

    Measured: Participants were followed from treatment until death or until principal investigator (PI) discretion. A median of 91.8 months.

  2. Number of Grades 1, 2, 3, 4, and/or 5 Serious Adverse Events Possibly and/or Probably Related to Treatment

    Here is the number of Grades 2, 3, 4, and/or 5 serious adverse events possibly and/or probably related to treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

    Measured: Time of registration through 6 years after the last treatment.

  3. Number of Grades 1, 2, 3, 4, and/or 5 Non-serious Adverse Events Possibly and/or Probably Related to Treatment

    Here is the number of Grades 1, 2, 3, 4, and/or 5 non-serious adverse events possibly and/or probably related to treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

    Measured: 30 days after end of treatment, up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2011 (estimated)
  2. Study start24 Mar 2011
  3. Primary completion10 Sep 2024
  4. Study completion10 Sep 2024

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01319565
Sponsor's protocol ID
110123
Other IDs
11-C-0123
Status last verified
Dec 2025
First submitted
18 Mar 2011
Last updated
19 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Publications

  • Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22.

    PubMed 18809613

  • Atkins 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 10561265

  • Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66. doi: 10.1093/jnci/86.15.1159.

    PubMed 8028037

  • Goff SL, Dudley ME, Citrin DE, Somerville RP, Wunderlich JR, Danforth DN, Zlott DA, Yang JC, Sherry RM, Kammula US, Klebanoff CA, Hughes MS, Restifo NP, Langhan MM, Shelton TE, Lu L, Kwong ML, Ilyas S, Klemen ND, Payabyab EC, Morton KE, Toomey MA, Steinberg SM, White DE, Rosenberg SA. Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma. J Clin Oncol. 2016 Jul 10;34(20):2389-97. doi: 10.1200/JCO.2016.66.7220. Epub 2016 May 23.

    PubMed 27217459

  • Seitter SJ, Sherry RM, Yang JC, Robbins PF, Shindorf ML, Copeland AR, McGowan CT, Epstein M, Shelton TE, Langhan MM, Franco Z, Danforth DN, White DE, Rosenberg SA, Goff SL. Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma. Clin Cancer Res. 2021 Oct 1;27(19):5289-5298. doi: 10.1158/1078-0432.CCR-21-1171.

    PubMed 34413159

  • Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015 Jan 15;75(2):296-305. doi: 10.1158/0008-5472.CAN-14-2277. Epub 2014 Nov 28.

    PubMed 25432172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aldesleukin, Cyclophosphamide and Fludarabine 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: finished, as of the sponsor's last update on 19 Dec 2025. 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 19 Dec 2025). 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?

Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) (time frame: Participants were followed from treatment to progression of disease or until principal investigator (PI) discretion (average 91.8 months).). 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 NCT01319565, which also lists 6 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 19 Dec 2025.

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