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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00871481
First received: March 27, 2009
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Biological: ipilimumab
Drug: cyclophosphamide
Procedure: biopsy
Biological: aldesleukin
Other: immunohistochemistry staining method
Genetic: polymerase chain reaction
Other: immunoenzyme technique
Biological: therapeutic allogeneic cytotoxic T lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: Phase I/II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 For Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Numeric frequency and functional persistence of transferred CTL [ Time Frame: Up to 6 months post-infusion ] [ Designated as safety issue: No ]
    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.

  • Toxicity assessment of study treatment, assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 6 months post-infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Responses to non-targeted T cell antigens [ Time Frame: Up to 1 year following T cell infusion and/or at the time of observed partial or complete clinical response ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 10
Study Start Date: February 2009
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (laboratory-treated T cells and ipilimumab)
Patients receive cyclophosphamide IV on day -2, therapeutic allogeneic 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.
Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Procedure: biopsy
Optional correlative studies
Other Name: biopsies
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Other: immunoenzyme technique
Correlative studies
Other Name: immunoenzyme techniques
Biological: therapeutic allogeneic cytotoxic T lymphocytes
Given IV
Other Name: therapeutic allogeneic CTLs

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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 allogeneic 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00871481

Locations
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
Investigators
Principal Investigator: Aude Chapuis Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00871481     History of Changes
Other Study ID Numbers: 2225.00, NCI-2010-00108, K12CA076930
Study First Received: March 27, 2009
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Aldesleukin
Interleukin-2
Antibodies
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014