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Metastatic MelanomaPhase 1NCT01955460

Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma

A Phase 1 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Metastatic Melanoma and Stage III Cutaneous Melanoma AJCC v7, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This pilot phase I trial studies the side effects and best dose of genetically modified T-cells followed by aldesleukin in treating patients with stage III-IV melanoma. T-cells are a type of white blood cell that help the body fight infections. Read more about this study

Who is it for?
Ages 12 to 70 years
What is being tested?
Aldesleukin, Cyclophosphamide and Fludarabine Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
15 Oct 2014to 30 Oct 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 12 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease (Turnstile I)
  • Patients must have a lesion amenable to resection or the collection of up to 5 needle core samples for the generation of TIL. (Turnstile I)
  • Patients must receive a magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) of the brain within 6 months of signing informed consent; if new lesions are present, patient must have definitive treatment; principal investigator (PI) or his designee should make final determination regarding enrollment (Turnstile I)
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 within 30 days of signing informed consent (Turnstile I)
  • Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible (Turnstile I)
  • Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability (Turnstile I)
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  • Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP); a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months) (Turnstile I)
  • Patients must have adequate TIL available (Turnstile II); pre-rapid expansion procedure (Pre-REP) TIL generated in the similar clinical trial 2004-0069 may also be utilized for Turnstile II
  • Patients must have at least one biopsiable measurable metastatic melanoma, lesion > or = to 1 cm (Turnstile II)
  • Patients may have brain lesions =< 1 cm each; the PI or designee will approve the treatment (Turnstile II)
  • Patients of both genders must practice birth control for four months after receiving the preparative regimen (lymphodepletion) and continue to practice birth control throughout the study; patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery (Turnstile II)
  • Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is an acceptable form of birth control (Turnstile II)
  • Patients with negative pregnancy test (urine or serum) must be documented within 14 days of screening for WOCBP; a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not menses at any time in the preceding 12 consecutive months) (Turnstile II)
  • Clinical performance status of ECOG 0-2 within 30 days of signing informed consent (Turnstile II)
  • Absolute neutrophil count greater than or equal to 1000/mm^3 (Turnstile II)
  • Platelet count greater than or equal to 100,000/mm^3 (Turnstile II)
  • Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II)
  • Serum alanine aminotransferase (ALT) less than three times the upper limit of normal (Turnstile II)
  • Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II)
  • Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (Turnstile II)
  • A stress cardiac test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II)
  • Pulmonary function tests (forced expiratory volume in one second [FEV1] > 65% or forced vital capacity [FVC] > 65% of predicted) within 6 months of lymphodepletion (Turnstile II)
  • MRI/CT/PET of the brain within 30 days of lymphodepletion (Turnstile II)

Who cannot join

  • Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; PI or his designee shall make the final determination regarding appropriateness of enrollment (Turnstile I)
  • Primary immunodeficiency and need for chronic steroid therapy, however prednisone is allowed at < 10 mg/day (Turnstile I)
  • Patients who are pregnant or nursing (Turnstile I)
  • Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent (Turnstile I)
  • Has had prior systemic cancer therapy within the past four weeks or v-raf murine sarcoma viral oncogene homolog B (B-RAF) or mitogen-activated protein kinase (MEK) inhibitors within 7 days at the time of the start of the lymphodepletion regimen (Turnstile II)
  • Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus (Turnstile II)
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  • Any active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, such as abnormal stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease; PI or his designee shall make the final determination regarding appropriateness of enrollment (Turnstile II)
  • Any form of primary or secondary immunodeficiency; must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm^3), white blood cell (WBC) (> 3,000/mm^3) or absence of opportunistic infections (Turnstile II)
  • Require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks prior to lymphodepletion; the exception being patients on chronic physiologic dose of steroid (Turnstile II)
  • Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated (Turnstile II)
  • Patients who are solid organ transplant recipients
  • Patients with prior bone marrow or stem cell transplantation

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With TGF-Beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

This pilot phase I trial studies the side effects and best dose of genetically modified T-cells followed by aldesleukin in treating patients with stage III-IV melanoma. T-cells are a type of white blood cell that help the body fight infections. Genes that may help the T-cells recognize melanoma cells are placed into the T-cells in the laboratory. Adding these genes to the T cells may help them kill more tumor cells when they are put back in the body. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells.

Read the detailed description

PRIMARY OBJECTIVES:

Primary for Cohort A:

  1. To assess the feasibility and safety of autologous transforming growth factor beta (TGFb) resistant (DNRII transduced) and NGFR transduced tumor infiltrating lymphocytes (TIL) in patients with metastatic melanoma.

Primary for Cohort B:

  1. To assess the feasibility and safety of autologous TGBβ resistant (DNRII transduced) TIL in patients with metastatic melanoma. Feasibility will be defined as the production of virally transduced T cells and treatment of patients with these cells

SECONDARY OBJECTIVES:

Secondary for Cohort A:

  1. To determine the survival and immune function of TGFb resistant (DNRII transduced) TIL in vivo.

II. To assess the anti-tumor effects of TGFb resistant (DNRII transduced) TIL.

Secondary for Cohort B:

  1. To determine the survival and immune function of TGFβ resistant (DNRII transduced) TIL in vivo

II. To assess the anti-tumor effects of TGFβ resistant (DNRII transduced) TIL.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).

After completion of study treatment, patients are followed up at 6 and 12 weeks, every 3 months for 1 year and then yearly for 10 years.

Being tested
Aldesleukin, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, NGFR-transduced Autologous T Lymphocytes
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NGFR-transduced Autologous T LymphocytesBiological

    Given IV

  • TGFbDNRII-transduced Autologous Tumor Infiltrating LymphocytesBiological

    Also called TGFbDNRII-transduced Autologous TILs

    Given IV

Study groups in NCT01955460
Study groupRoleWhat they receive
Treatment (chemotherapy, autologous T-cell immunotherapy)ExperimentalPatients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).
Receives: Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: NGFR-transduced Autologous T Lymphocytes; Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes

What is being measured

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

  1. (Cohort A) Generation of TGF alpha (TGFa)-DNRII and NGFR transduced tumor infiltrating lymphocytes (TILs)

    Feasibility of generating TGFa-DNRII and NGFR transduced TILs and safety of treating patients with genetically modified T cells will be assessed. Feasibility will be defined as the production of virally transduced T cells and treatment of patients with these cells.

    Measured: Up to 5 years

  2. (Cohort B) The primary endpoint of growing enough TIL for patient treatment and sample size is 15 patients.

    The primary endpoint is feasibility (F) of growing enough TIL for patient treatment and sample size is 15 patients.) If you assume that Prob(F) follows 2s a non-informative beta (0.50, 0.50)prior, which has mean = 0.50 and effective sample size =1, then for example, if you observe 5/15 patients for whom F occurred and 10/15 for whom it did not, then a posterior 95% credible interval for Prob(F) would have lower and upper limits 0.14 to 0.58.

    Measured: Up to 6 months

Secondary outcomes (4)

  1. (Cohort A) Response

    Will be defined following immune-related response criteria as a 50% or greater decrease in the tumor's linear dimension post treatment compared to baseline.

    Measured: Up to 24 months

  2. (Cohort A) Number of DNRII transduced cells

    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a generalized linear mixed model (GLMM) approach may be used to model the DNRII/NGFR ratio over time.

    Measured: 6 months

  3. (Cohort A) Number of NGFR transduced cells at infusion

    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a GLMM approach may be used to model the DNRII/NGFR ratio over time.

    Measured: Day 0

  4. (Cohort A) Number of NGFR transduced cells based on tumor biopsy

    A linear regression model will be used to test the hypothesis that the DNRII cells are more likely to survive longer in the tumor environment than the NGFR (control) cells. Dose will be included as a covariate. Separate analyses will be performed at each post-treatment time point (6 weeks, 12 weeks, 6 months, 12 months, and 24 months), with the 6-month time point considered primary. If there is evidence of a linear relationship over time, a GLMM approach may be used to model the DNRII/NGFR ratio over time.

    Measured: Up to 24 months

Timeline

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

  1. First posted7 Oct 2013 (estimated)
  2. Study start15 Oct 2014
  3. Primary completion30 Oct 2027 (estimated)
  4. Study completion30 Oct 2027 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01955460
Sponsor's protocol ID
2012-0758
Other IDs
NCI-2014-01211, RP110553-P4, RM1012-012-1, 2012-0758
Status last verified
Oct 2026
First submitted
27 Sep 2013
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Metastatic Melanoma and Stage III Cutaneous Melanoma AJCC v7, run by M.D. Anderson Cancer Center 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 23 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. 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 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?

This study is still under way. Results are not available in the source record yet.

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?

(Cohort A) Generation of TGF alpha (TGFa)-DNRII and NGFR transduced tumor infiltrating lymphocytes (TILs) (time frame: Up to 5 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 NCT01955460.

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 6 Oct 2026.

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