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

NCT00871481 | Completed Phase 1 DMC

• 3 other identifiers: 2225.00NCI-2010-00108K12CA076930
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 6 months post-infusion

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

  Up to 6 months post-infusion

Secondary Outcomes (1)

• Responses to non-targeted T cell antigens

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

Study Arms (1)

Treatment (laboratory-treated T cells and ipilimumab)

EXPERIMENTAL

Patients 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.

Biological: ipilimumab; Drug: cyclophosphamide; Procedure: biopsy; Biological: aldesleukin; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Other: immunoenzyme technique; Biological: therapeutic cytotoxic T lymphocytes

Interventions

ipilimumab BIOLOGICAL

Given IV

Also known as: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

Treatment (laboratory-treated T cells and ipilimumab)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (laboratory-treated T cells and ipilimumab)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (laboratory-treated T cells and ipilimumab)

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (laboratory-treated T cells and ipilimumab)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (laboratory-treated T cells and ipilimumab)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment (laboratory-treated T cells and ipilimumab)

immunoenzyme technique OTHER

Correlative studies

Also known as: immunoenzyme techniques

Treatment (laboratory-treated T cells and ipilimumab)

therapeutic cytotoxic T lymphocytes BIOLOGICAL

Given IV

Also known as: therapeutic CTLs

Treatment (laboratory-treated T cells and ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 27269940 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Cyclophosphamide; Biopsy; aldesleukin; Interleukin-2; Immunohistochemistry; Polymerase Chain Reaction; Immunoenzyme Techniques

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Histocytochemistry; Histological Techniques; Immunologic Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques; Immunoassay; Molecular Probe Techniques

Study Officials

• Aude Chapuis

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 27, 2009
• First Posted: March 30, 2009
• Study Start: February 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (1)