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

NCT03068624 | Unknown Phase 1 FDA Drug

• 2 other identifiers: 2016-0414NCI-2018-01291
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). To make specialized CD8+ T cells, researchers separate out T cells collected from patients' blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patients. This is known as "adoptive T cell transfer" or "adoptive T cell therapy." Drugs used in chemotherapy, such as cyclophosphamide, may 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. 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. Giving autologous CD8+ SLC45A2-specific T lymphocytes together with cyclophosphamide, aldesleukin, and ipilimumab may work better in treating patients with metastatic uveal melanoma.

Conditions

Metastatic Malignant Neoplasm in the Liver; Metastatic Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  As determined by dose limiting toxicity (DLT). MTD defined at the highest dose at which no more than 1 in 6 patients has experienced DLT.

  Up to 6 weeks

Secondary Outcomes (7)

• Overall response rate

  Up to 5 years

• Duration of clinical response (DOR)

  From the start of study treatment up to 5 years

• Persistence of in vivo T cells and non-target antigen recognition

  From the start of study treatment up to 5 years

• Overall survival (OS)

  From the start of study treatment up to 5 years

• Progression-free survival (PFS)

  From the start of study treatment up to 5 years

Study Arms (1)

Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive cyclophosphamide IV over 30-60 minutes on day -2. T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin BID SC for 14 days in the absence of disease progression or unacceptable toxicity. POST T-CELL INFUSION: Patients receive 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+ SLC45A2-specific T Lymphocytes; Drug: Cyclophosphamide; Biological: Ipilimumab

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 (cyclophosphamide, T-cells, aldesleukin, ipilimumab)

Autologous CD8+ SLC45A2-specific T Lymphocytes BIOLOGICAL

Given via hepatic arterial infusion via central catheter

Also known as: Autologous SLC45A2-specific CTLs, Autologous SLC45A2-specific Cytotoxic T Lymphocytes

Treatment (cyclophosphamide, T-cells, 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 (cyclophosphamide, T-cells, aldesleukin, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

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

Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• PHERESIS (TURNSTILE 1): Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease or high-risk primary uveal melanoma defined as a recurrence score of \> 50% in 5 years. A diagnosis of uveal melanoma can be made clinically without primary tissue evaluation, based on history and records. A prior history of brachytherapy to the eye is sufficient clinical support for a diagnosis of uveal melanoma.
• PHERESIS (TURNSTILE 1): Hematocrit (HCT) \>= 24% or hemoglobin (HB) \>= 8 g/dL.
• PHERESIS (TURNSTILE 1): Platelets \> 50,000.
• PHERESIS (TURNSTILE 1): Expression of human leukocyte antigen (HLA)-A:0201 or HLA-A:2402.
• PHERESIS (TURNSTILE 1): Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of 0-1.
• PHERESIS (TURNSTILE 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 completion of the study. 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.
• PHERESIS (TURNSTILE 1): Male patients must be willing and able to use an acceptable method of birth control, during and for at least 3 months after completion of the study, if their sexual partners are WOCBP.
• PHERESIS (TURNSTILE 1): Willing and able to give informed consent.
• PHERESIS (TURNSTILE 1): Toxicity related to prior therapy must either have returned to =\< grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the principal investigator (PI).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): ECOG/Zubrod performance status of 0-1 (evaluate at least 1 week before T cell infusion).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging per irRC (evaluate at least 1 week before T cell infusion).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): At least 4 weeks must have elapsed since the last chemotherapy, targeted therapy, immunotherapy, radiotherapy, liver-directed therapy, 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 (evaluate at least 1 week before T cell infusion).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): For the ipilimumab cohort only: Toxicity related to prior therapy must either have returned to =\< grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the PI (evaluate at least 1 week before T cell infusion).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Patients must have liver metastasis (evaluate at least 1 week before T cell infusion).
• T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 3 months after completion of study (evaluate at least 1 week before T cell infusion).

You may not qualify if:

• PHERESIS: Secondary malignancy is allowed providing it does not require concurrent therapy.
• PHERESIS: 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 pheresis.
• PHERESIS: Significant cardiovascular abnormalities as defined by any one of the following:
• Congestive heart failure
• Clinically significant hypotension
• Symptoms of coronary artery disease (angina, dyspnea)
• Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
• PHERESIS: 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.
• PHERESIS: Positive screening tests for human immunodeficiency virus (HIV), hepatitis B virus (Hep B), and hepatitis C virus (Hep C). If positive results are not indicative of true active or chronic infection, the patient can be treated.
• PHERESIS: Participation in any other immunotherapy treatment, that in the opinion of the principal investigator would be unsafe to receive further checkpoint blockade immunotherapy
• White blood cell (WBC) =\< 2000/uL (prior to cyclophosphamide and T cell infusions).
• Hct =\< 24% or Hb =\< 8 g/dL (prior to cyclophosphamide and T cell infusions).
• Absolute neutrophil count (ANC) =\< 1000 (prior to cyclophosphamide and T cell infusions).
• Platelets =\< 50,000 (prior to cyclophosphamide and T cell infusions).
• Creatinine \>= 3.0 x upper limit of normal (ULN) (prior to cyclophosphamide and T cell infusions).

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

• MD Anderson Cancer Center

MeSH Terms

Conditions

Uveal Melanoma

Interventions

aldesleukin; Cyclophosphamide; Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal 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

Study Officials

• Sapna P Patel

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2017
• First Posted: March 3, 2017
• Study Start: September 8, 2017
• Primary Completion: December 31, 2022
• Study Completion: July 31, 2025
• Last Updated: January 25, 2024

Record last verified: 2024-01

Locations

US (1)