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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-22

Study Completion Date

2024-04-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Metastatic Melanoma

NCT01106235

Stage IV Melanoma

TERMINATED PHASE1

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

NCT00871481

Recurrent Melanoma Stage IV Melanoma

COMPLETED PHASE1/PHASE2

Genetically Modified T-Cells Followed by Aldesleukin in Treating Patients With Stage III-IV Melanoma

NCT01955460

Metastatic Melanoma Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 +3 more

ACTIVE_NOT_RECRUITING PHASE1

Biological Therapy in Treating Patients With Metastatic Melanoma

NCT00002786

Melanoma (Skin)

COMPLETED PHASE1/PHASE2

Autologous CD8+ SLC45A2-Specific T Lymphocytes With Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Uveal Melanoma

NCT03068624

Metastatic Malignant Neoplasm in the Liver Metastatic Uveal Melanoma

ACTIVE_NOT_RECRUITING PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Metastatic Melanoma Stage IV Cutaneous Melanoma AJCC v6 and v7

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given SC

Autologous CD8+ Melanoma Specific T Cells

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Aldesleukin

Given SC

Intervention Type BIOLOGICAL

Autologous CD8+ Melanoma Specific T Cells

Given IV

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Ipilimumab

Given IV

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

125-L-Serine-2-133-interleukin 2 Proleukin r-serHuIL-2 Recombinant Human IL-2 Recombinant Human Interleukin-2 Autologous Melanoma Specific Cytotoxic T Lymphocytes (-)-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 Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No