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Therapeutic Autologous Lymphocytes, Aldesleukin, and Denileukin Diftitox in Treating Patients With Stage III-IV Melanoma

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ClinicalTrials.gov Identifier: NCT00945269
Recruitment Status : Terminated (ONTAK has been pulled off the market for further testing. Subsequently, EISAI will no longer be supporting clinical trials that utilize this drug.)
First Posted : July 24, 2009
Last Update Posted : December 8, 2011
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sylvia Lee, Fred Hutchinson Cancer Research Center

Brief Summary:

RATIONALE: White blood cells that have been treated in a laboratory may be able to kill tumor cells in patients with melanoma. Aldesleukin and denileukin diftitox may stimulate the white blood cells to kill melanoma cells. Giving therapeutic autologous lymphocyte therapy together with aldesleukin and denileukin diftitox may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving therapeutic autologous lymphocytes together with aldesleukin and denileukin diftitox and to see how well it works in treating patients with stage III-IV melanoma

Condition or disease Intervention/treatment Phase
Recurrent Melanoma Stage III Melanoma Stage IV Melanoma Biological: therapeutic autologous lymphocytes Biological: aldesleukin Biological: denileukin diftitox Procedure: biopsy Other: immunohistochemistry staining method Other: laboratory biomarker analysis Genetic: polymerase chain reaction Phase 1 Phase 2

Detailed Description:


I. Assess the safety of cellular adoptive immunotherapy in melanoma patients using autologous CD8+ antigen-specific T-cell clones following CD25 lymphodepletion.

II. Determine the influence of CD25 lymphodepletion on the duration of in vivo persistence of adoptively transferred CD8+ antigen-specific cytotoxic T-cell (CTL) clones.


I. Assess the anti-tumor efficacy of cellular adoptive immunotherapy in melanoma patients using autologous CD8+ antigen-specific T cell clones following CD25 lymphodepletion.

II. Evaluate the induction of T cells to non-targeted tumor-associated antigens (antigen-spreading) following adoptive transfer of CD8+ antigen-specific CTL and CD25 lymphodepletion.

OUTLINE: This is a phase I study followed by a phase II study.

Patients receive autologous T-cell intravenously (IV) over 30-60 minutes on days 0 and 28 and low-dose aldesleukin subcutaneously (SC) twice daily on days 0 to 13 and 28 to 41. Beginning 4-6 days before second T- cell infusion, patients receive denileukin diftitox IV over 30 minutes on days 1-3. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and then every 3 months thereafter.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study To Evaluate The Safety Of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following CD25 Lymphodepletion For Patients With Metastatic Melanoma
Study Start Date : July 2009
Primary Completion Date : January 2011
Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Aldesleukin
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment (cellular adoptive immunotherapy)
Patients receive autologous T-cell IV over 30-60 minutes on days 0 and 28 and low-dose aldesleukin SC twice daily on days 0 to 13 and 28 to 41. Beginning 4-6 days before second T-cell infusion, patients receive denileukin diftitox IV over 30 minutes on days 1-3.
Biological: therapeutic autologous lymphocytes
Given IV
Other Names:
  • AL
  • Autologous Lymphocytes
  • autologous T cells
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Biological: denileukin diftitox
Given IV
Other Names:
  • DAB389 interleukin-2
  • DAB389 interleukin-2 immunotoxin
  • DAB389-IL2
  • DABIL2
Procedure: biopsy
Optional correlative studies
Other Name: biopsies
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: laboratory biomarker analysis
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR

Primary Outcome Measures :
  1. In vivo survival of CD8+ transferred T-clones [ Time Frame: Days +0, 1, 3, 7, 14, 22, 28, 29, 31, 35, 42, 49, 56, 63, 70, 77, 84 ]
    The design of this trial using the first infusion of CD8 T cells administered alone as a baseline for each patient permits intra-patient analysis using paired samples with increased statistical power.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histopathological documentation of melanoma
  • Expression of human leukocyte antigen (HLA)-A2 or B44 as determined by HLA typing lab
  • Patients whose tumor expresses targeted antigen and restricting allele against which CD8 T cell clones can be generated
  • Karnofsky Performance status of at least 80% and an expected survival of greater than 6 months
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan)
  • Normal cardiac stress test (treadmill, echocardiogram, or myocardial perfusion scan) within 182 days prior to enrollment is required of patients with a history of cardiac disease
  • Pulse > 45 or < 120
  • Weight >= 45 kg
  • Temperature =< 38C (< 100.4 F)
  • White blood cells (WBC) >= 3,000
  • Hematocrit (HCT) >= 30%
  • Platelets >= 100,000
  • Patients must be willing and able to discontinue the use of all antihypertensive medications 24 hours prior to and during IL2 therapy

Exclusion Criteria:

  • Pregnant women, nursing mothers, or women of reproductive ability who are unwilling to use effective contraception or abstinence
  • Serum creatinine > 1.6mg/dL
  • Creatinine clearance < 75 ml/min
  • Aspartate aminotransferase (AST) > 2.5 x upper limit of normal
  • Alanine aminotransferase (ALT) > 2.5 x upper limit of normal
  • Bilirubin > 1.6 or international normalized ratio (INR) > 1.5 due to hepatic dysfunction
  • Albumin < 3.0g/dL
  • 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) < 80% predicted or diffusing capacity of the lung for carbon monoxide (DLco) (corr for hemoglobin [Hgb]) < 75% will be excluded
  • Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, symptoms of coronary artery disease
  • Symptomatic central nervous system (CNS) metastases greater than 1 cm at time of therapy; patients with 1-2 asymptomatic, less than 1cm brain/CNS metastases without significant edema may be considered for treatment
  • Patients with active infections or oral temperature > 38.2 C within 48 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
  • Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy)
  • Concurrent treatment with steroids
  • Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
  • The following agents are not allowed while on study: systemic corticosteroids (except as outlined for management of toxicity of nontransduced CTL), immunotherapy (for example, interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, expanded polyclonal TIL or LAK therapy), pentoxifylline, or other investigational agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00945269

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Sylvia Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Responsible Party: Sylvia Lee, Research Associate, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00945269     History of Changes
Other Study ID Numbers: 2271.00
NCI-2010-00738 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
K12CA076930 ( U.S. NIH Grant/Contract )
R21CA137647 ( U.S. NIH Grant/Contract )
First Posted: July 24, 2009    Key Record Dates
Last Update Posted: December 8, 2011
Last Verified: December 2011

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Denileukin diftitox
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents