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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02027935
Recruitment Status : Active, not recruiting
First Posted : January 6, 2014
Last Update Posted : May 24, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Stage IV Cutaneous Melanoma AJCC v6 and v7 Biological: Aldesleukin Biological: Autologous CD8+ Melanoma Specific T Cells Drug: Cyclophosphamide Biological: Ipilimumab Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 for Patients With Metastatic Melanoma
Actual Study Start Date : January 22, 2015
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2023


Arm Intervention/treatment
Experimental: Treatment (T cells, chemo, aldesleukin, ipilimumab)
Beginning 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.
Biological: Aldesleukin
Given SC
Other Names:
  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2

Biological: Autologous CD8+ Melanoma Specific T Cells
Given IV
Other Name: Autologous Melanoma Specific Cytotoxic T Lymphocytes

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Overall response [ Time Frame: Up to 12 weeks ]
    Monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung.

  2. Incidence of toxicity [ Time Frame: Up to 5 years ]
    Monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • EXCLUSION FOR ENROLLMENT
  • 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
  • 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
  • EXCLUSION CRITERIA FOR TREATMENT
  • 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

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): NCT02027935


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Adi Diab M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02027935    
Other Study ID Numbers: 2012-1055
NCI-2014-01040 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2012-1055 ( Other Identifier: M D Anderson Cancer Center )
P50CA159981 ( U.S. NIH Grant/Contract )
First Posted: January 6, 2014    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Aldesleukin
Cyclophosphamide
Ipilimumab
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents