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Recurrent MelanomaPhase 1/2NCT00871481

Laboratory-Treated T Cells and Ipilimumab in Treating Patients With Metastatic Melanoma

A Phase 1/2 study testing ipilimumab, cyclophosphamide and biopsy in people with Recurrent Melanoma and Stage IV Melanoma, run by Fred Hutchinson 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 I/II trial is studying the side effects of giving laboratory-treated T cells and ipilimumab together to see how well they work in treating patients with metastatic melanoma. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Melanoma, Stage IV Melanoma
What is being tested?
ipilimumab, cyclophosphamide and biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Feb 2009to Oct 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • 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
  • 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 or 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
  • Willing and able to give informed consent
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  • Adequate venous access-consider peripherally inserted central catheter (PICC) or central line
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
  • 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

Who cannot join

  • Patients with active infections or oral temperature > 38.2 C within 72 hours prior to planned leukapheresis; the procedure may be deferred
  • Patients with hematocrit (Hct) < 30%, white blood cells (WBC) < 2500/uL and platelets < 50,000 immediately prior to leukapheresis; the procedure may be deferred
  • 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
  • White blood cell count (WBC) < 2000/uL
  • Hematocrit (Hct) < 24% or hemoglobin (Hb) < 8 g/dL
  • Absolute neutrophile count (ANC) < 1000
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  • Platelets < 50,000
  • Creatinine > 3.0 x upper limit normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN
  • Bilirubin > 3 x ULN
  • 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
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusion capacity of carbon monoxide (DLco) (corr for Hgb) < 50% will be excluded
  • Significant cardiovascular abnormalities as defined by any one of the following:
  • Congestive heart failure
  • Clinically significant hypotension
  • Symptoms of coronary artery disease
  • Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
  • Ejection fraction < 50 % (echocardiogram or multi gated acquisition [MUGA] scan)
  • Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging [MRI] or contrast CT)
  • 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 (Hep) B, and Hep C; if positive results are not indicative of true active or chronic infection, the patient can be treated
  • Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy
  • No prisoners or children will be enrolled on this study
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

This phase I/II trial is studying the side effects of giving laboratory-treated T cells and ipilimumab together to see how well they work in treating patients with metastatic melanoma. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving laboratory-treated T cells together with ipilimumab may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

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

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

SECONDARY OBJECTIVES:

  1. 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:

Patients receive cyclophosphamide intravenously (IV) on day -2, therapeutic cytotoxic T lymphocytes IV over 30-60 minutes on day 0, low-dose 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 periodically.

Medical subject headings
Melanoma

What participants receive

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

  • ipilimumabBiological

    Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • biopsyProcedure or surgery

    Also called biopsies

    Optional correlative studies

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given SC

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative studies

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • immunoenzyme techniqueOther

    Also called immunoenzyme techniques

    Correlative studies

  • therapeutic cytotoxic T lymphocytesBiological

    Also called therapeutic CTLs

    Given IV

Study groups in NCT00871481
Study groupRoleWhat they receive
Treatment (laboratory-treated T cells and ipilimumab)ExperimentalPatients receive cyclophosphamide IV on day -2, therapeutic cytotoxic T lymphocytes IV over 30-60 minutes on day 0, low-dose 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: ipilimumab; Drug: cyclophosphamide; Procedure: biopsy; Biological: aldesleukin; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Other: immunoenzyme technique; Biological: therapeutic cytotoxic T lymphocytes

What is being measured

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

  1. Numeric frequency and functional persistence of transferred CTL

    Determined using peptide major histocompatibility complex (MHC)-tetramer analysis or specific CDR3 T-cell-receptor (TCR) quantitative polymerase chain reaction (PCR) of transferred CTL if necessary. The function of transferred CTL will be determined by intracellular cytokine staining of tetramer+ CD8+ cells following in vitro stimulation.

    Measured: Up to 6 months post-infusion

  2. Toxicity assessment of study treatment, assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

    Measured: Up to 6 months post-infusion

Secondary outcomes (1)

  1. Responses to non-targeted T cell antigens

    Blood samples taken will be analyzed for the induction of non-targeted T cell responses. Two approaches will be used: tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assay.

    Measured: Up to 1 year following T cell infusion and/or at the time of observed partial or complete clinical response

Timeline

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

  1. First posted30 Mar 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionSep 2013
  4. Study completionOct 2013

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
Single blind
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00871481
Sponsor's protocol ID
2225.00
Other IDs
NCI-2010-00108, K12CA076930
Status last verified
Apr 2017
First submitted
27 Mar 2009
Last updated
19 Apr 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Chapuis AG, Roberts IM, Thompson JA, Margolin KA, Bhatia S, Lee SM, Sloan HL, Lai IP, Farrar EA, Wagener F, Shibuya KC, Cao J, Wolchok JD, Greenberg PD, Yee C. T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression. J Clin Oncol. 2016 Nov 1;34(31):3787-3795. doi: 10.1200/JCO.2015.65.5142.

    PubMed 27269940

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ipilimumab, cyclophosphamide and biopsy in people with Recurrent Melanoma and Stage IV Melanoma, run by Fred Hutchinson 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 11 inclusion and 26 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 Apr 2017. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Numeric frequency and functional persistence of transferred CTL (time frame: Up to 6 months post-infusion). 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 NCT00871481, which also lists 1 linked publication.

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 Apr 2017.

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