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Metastatic MelanomaPhase 1/2NCT01740557

Genetically Modified Therapeutic Autologous Lymphocytes Followed by Aldesleukin in Treating Patients With Stage III or Metastatic Melanoma

A Phase 1/2 study testing Aldesleukin, CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes and Cyclophosphamide 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.

Completed

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

Official record
Search all trials

Trial summary

This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
28 Jan 2015to 21 Apr 2023
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • TURNSTILE I INCLUSION CRITERIA:
  • 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 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 will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee
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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 (Turnstile I)
  • CHEMOTHERAPY/CELL INFUSION INCLUSION CRITERIA:
  • Patients must have adequate TIL available (Turnstile II)
  • Patients must have at least one biopsiable and measurable metastatic melanoma lesions >= 1 cm (Turnstile II)
  • Patients may have brain lesions which measure =< 1 cm each (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)
  • Pregnancy testing will be performed within 14 days prior to treatment (Turnstile II)
  • Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (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 transaminase (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 multigated acquisition [MUGA] scan, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II)
  • Forced expiratory volume in 1 second (FEV1) > 65% of predicted within 6 months of lymphodepletion (Turnstile II) 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

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)
  • Patients who are pregnant or nursing (Turnstile I)
  • CHEMOTHERAPY/CELL INFUSION EXCLUSION CRITERIA:
  • Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen (Turnstile II)
  • Women who are pregnant will be excluded (Turnstile II)
  • 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)
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  • 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)
  • Requires no steroids within 4 weeks and have not 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)

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 T -Cells Transduced With CXCR2 and NGFR Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the feasibility and safety of CXCR2 and NGFR transduced tumor-infiltrating lymphocytes (TIL) for treating metastatic malignant melanoma.

SECONDARY OBJECTIVES:

  1. Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors.

II. Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL.

III. Characterize the clinical response and correlate with migration of CXCR2 transduced TIL to the tumor and levels of CXCL1 and CXCL8 at the tumor site.

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 CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL 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 weeks 6 and 12, every 3 months for a year, and then annually for up to 15 years.

Being tested
Aldesleukin, CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis
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

  • CXCR2-transduced Autologous Tumor Infiltrating LymphocytesBiological

    Also called CXCR2-transduced Autologous TILs

    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

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT01740557
Study groupRoleWhat they receive
Treatment (genetically modified T-cells, high-dose aldesleukinExperimentalPatients 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 CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL 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; Biological: CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: NGFR-transduced Autologous T Lymphocytes; Other: Quality-of-Life Assessment

What is being measured

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

  1. Number of Participants With Immune-Related Response

    Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline.

    Response will be evaluated by positron emission tomography or computed tomography imaging.

    Measured: Up to 1 year

  2. Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities

    Possible grade 3 or worse toxicities not normally associated with lymphodepletion and high dose IL-2 will be reported.

    Measured: Up to 8 weeks

Secondary outcomes (3)

  1. CXCR2 Transduction

    Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. his is a statistical version of the intuitive idea that, if the TIL methodology works as designed and the genetically transduced T-cells differentially recognize the cancer cell cytokines, then the ratio of post- and pre-treatment ratios RR = RY/RX should be larger than 1.

    Measured: At infusion

  2. CXCL1 and CXCL8 Chemokines Produced

    Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL

    Measured: At infusion

  3. Characterize the Clinical Response and Correlate With Migration of CXCR2 Transduced TIL to the Tumor and Levels of CXCL1 and CXCL8 at the Tumor Site.

    Measured: At infusion

Timeline

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

  1. First posted4 Dec 2012 (estimated)
  2. Study start28 Jan 2015
  3. Primary completion21 Apr 2023
  4. Study completion21 Apr 2023

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01740557
Sponsor's protocol ID
2009-0471
Other IDs
NCI-2014-02655, 2009-0471, R01CA116206
Status last verified
Sep 2024
First submitted
30 Nov 2012
Last updated
8 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aldesleukin, CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes and Cyclophosphamide 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 25 inclusion and 9 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 8 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 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 8 Oct 2024). 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?

Number of Participants With Immune-Related Response (time frame: Up to 1 year). 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 NCT01740557.

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 8 Oct 2024.

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