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Metastatic MelanomaPhase 2NCT02027935

CD8+ Antigen-Specific T Cells, Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Melanoma

A Phase 2 study testing Aldesleukin, Autologous CD8+ Melanoma Specific T Cells and Cyclophosphamide in people with Metastatic Melanoma and Stage IV Cutaneous Melanoma AJCC v6 and 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
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Trial summary

This phase II trial studies the side effects and how well white blood cells taken from person's own (autologous) cluster of differentiation (CD)8+ antigen-specific T cells, cyclophosphamide, aldesleukin, and ipilimumab work in treating patients with melanoma that has spread to another place in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, Autologous CD8+ Melanoma Specific T Cells and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
22 Jan 2015to 12 Apr 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ELIGIBILITY FOR ENROLLMENT
  • Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease
  • Expression of human leukocyte antigen (HLA)-A2
  • Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of '0-1' at screening visit
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized; suggested precautions should be used to minimize the risk of pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
  • Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP
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  • Willing and able to give informed consent
  • Adequate venous access - consider peripherally inserted central catheter (PICC) or central line
  • Evaluation of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600 mutation status
  • Measurable tumor (by Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
  • Melan-A (MART) 1 or solute carrier family 45, member 2 (SLC45A2) (+) staining results; (if patients have not had staining test in the past, the test will be run after patient consent is obtained, but before enrollment)
  • ELIGIBILITY FOR TREATMENT (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2)
  • ECOG/Zubrod performance status of '0-1'
  • At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery; at least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin; if started before T-cell administration, ipilimumab infusions must be least 21 days apart
  • Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible
  • Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped
  • Willing and able to give informed consent.

Who cannot join

  • Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix
  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry
  • Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging [MRI] or contrast computed tomography [CT])
  • No signs or symptoms of CNS metastases (mets) within the last 30 days (from enrollment evaluation)
  • No single lesion larger than 1 cm
  • No more than 5 lesions
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  • Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the investigator to be unacceptable
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
  • Positive screening tests for human immunodeficiency virus (HIV), hepatitis B (hep B), and hepatitis C (hep C) (referencing blood draw at leukapheresis screening); if positive results are not indicative of true active or chronic infection, the patient can be treated
  • White blood cells (WBC) =< 1000/uL
  • Hematocrit (Hct) =< 24% or hemoglobin (Hb) =< 8 g/dL
  • Absolute neutrophil count (ANC) =< 500
  • Platelets =< 50,000
  • Creatinine >= 3.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >= 2.5 x ULN
  • Bilirubin >= 3 x ULN
  • Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy
  • Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose
  • Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study
  • WBC =< 1000/uL (prior to cyclophosphamide and T cell infusions)
  • Hct =< 24% or hemoglobin =< 8 g/dL (prior to cyclophosphamide and T cell infusions)
  • ANC =< 500 (prior to cyclophosphamide and T cell infusions)
  • Platelets =< 50,000 (prior to cyclophosphamide and T cell infusions)
  • Creatinine >= 3.0 x ULN (prior to cyclophosphamide and T cell infusions)
  • AST/ALT >= 2.5 x ULN (prior to cyclophosphamide and T cell infusions)
  • Bilirubin >= 3 x ULN (prior to cyclophosphamide and T cell infusions)
  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
  • Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy.
  • Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
  • Patients may not be on any other treatments for their cancer aside from those included in the protocol. Patients may not undergo another form of treatment concurrently with this study.
  • Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening MRI or contrast CT):
  • No signs or symptoms of CNS mets within the last 30 days (from enrollment evaluation).
  • No single lesion larger than 1cm
  • No more than 5 lesions

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: Phase II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 for Patients With Metastatic Melanoma

This phase II trial studies the side effects and how well white blood cells taken from person's own (autologous) cluster of differentiation (CD)8+ antigen-specific T cells, cyclophosphamide, aldesleukin, and ipilimumab work in treating patients with melanoma that has spread to another place in the body. Autologous CD8+ antigen-specific T cells are white blood cells that are designed in the laboratory to find melanoma cells and may kill them. Biological therapies, such as aldesleukin, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving autologous CD8+ antigen-specific T cells with cyclophosphamide, aldesleukin, and ipilimumab may be an effective treatment for patients with metastatic melanoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Evaluate the safety and efficacy of adoptively transferred cytotoxic T-lymphocytes (CTL) targeting melanoma tumors combined with anti-CTLA4.

SECONDARY OBJECTIVES:

  1. Evaluate the influence of anti-CTLA4 on the duration of in vivo persistence and anti-tumor efficacy achieved following adoptive transfer of antigen-specific CTL.

II. Evaluate the influence of anti-CTLA4 on the induction of T cells to non-targeted tumor-associated antigens (antigen-spreading) following adoptive transfer antigen-specific CTL, and the correlation of these responses with clinical outcome.

OUTLINE:

Beginning 48 to 72 hours prior to T cell infusion, patients receive cyclophosphamide intravenously (IV) over 30-60 minutes. Patients then receive autologous CD8+ melanoma-specific T cells IV over 30-60 minutes on day 0, aldesleukin subcutaneously (SC) twice daily (BID) on days 0-13 and ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Being tested
Aldesleukin, Autologous CD8+ Melanoma Specific T Cells, Cyclophosphamide, Ipilimumab, 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 SC

  • Autologous CD8+ Melanoma Specific T CellsBiological

    Also called Autologous Melanoma Specific Cytotoxic T Lymphocytes

    Given IV

  • CyclophosphamideDrug

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

    Given IV

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02027935
Study groupRoleWhat they receive
Treatment (T cells, chemo, aldesleukin, ipilimumab)ExperimentalBeginning 48 to 72 hours prior to T cell infusion, patients receive cyclophosphamide IV over 30-60 minutes. Patients then receive autologous CD8+ melanoma-specific T cells IV over 30-60 minutes on day 0, aldesleukin SC BID on days 0-13 and ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Aldesleukin; Biological: Autologous CD8+ Melanoma Specific T Cells; Drug: Cyclophosphamide; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. CTL With Anti-CTLA4

    Evaluate the safety and efficacy of adoptively transferred CTL targeting melanoma tumors combined with anti-CTLA4

    Measured: Baseline up to 2 years

Secondary outcomes (1)

  1. Anti-CTLA4 Duration

    Evaluate the influence of anti-CTLA4 on the duration of in vivo persistence and anti-tumor efficacy achieved following adooptive transfer of antigen-specific CTL.

    Measured: Baseline up to 2 years

Timeline

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

  1. First posted6 Jan 2014 (estimated)
  2. Study start22 Jan 2015
  3. Primary completion12 Apr 2024
  4. Study completion12 Apr 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02027935
Sponsor's protocol ID
2012-1055
Other IDs
NCI-2014-01040, 2012-1055, P50CA159981
Status last verified
Sep 2024
First submitted
2 Jan 2014
Last updated
8 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aldesleukin, Autologous CD8+ Melanoma Specific T Cells and Cyclophosphamide in people with Metastatic Melanoma and Stage IV Cutaneous Melanoma AJCC v6 and 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 17 inclusion and 34 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 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 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?

CTL With Anti-CTLA4 (time frame: Baseline up to 2 years). 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 NCT02027935.

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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