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

NCT02027935 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2012-1055NCI-2014-01040P50CA159981
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• CTL With Anti-CTLA4

  Evaluate the safety and efficacy of adoptively transferred CTL targeting melanoma tumors combined with anti-CTLA4

  Baseline up to 2 years

Secondary Outcomes (1)

• Anti-CTLA4 Duration

  Baseline up to 2 years

Study Arms (1)

Treatment (T cells, chemo, aldesleukin, ipilimumab)

EXPERIMENTAL

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; Biological: Autologous CD8+ Melanoma Specific T Cells; Drug: Cyclophosphamide; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (T cells, chemo, aldesleukin, ipilimumab)

Autologous CD8+ Melanoma Specific T Cells BIOLOGICAL

Given IV

Also known as: Autologous Melanoma Specific Cytotoxic T Lymphocytes

Treatment (T cells, chemo, aldesleukin, ipilimumab)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (T cells, chemo, aldesleukin, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (T cells, chemo, aldesleukin, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (T cells, chemo, aldesleukin, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Cyclophosphamide; Ipilimumab; CTLA-4 Antigen

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; 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

Results Point of Contact

• Title: Dr. Adi Diab
• Organization: University of Texas MD Anderson Cancer Center

adiab@mdanderson.org

(713) 745-7336

Study Officials

• Adi Diab

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2014
• First Posted: January 6, 2014
• Study Start: January 22, 2015
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-09

Locations

US (1)