Genetically Modified Therapeutic Autologous Lymphocytes Followed by Aldesleukin in Treating Patients With Stage III or 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

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-28

Study Completion Date

2023-04-21

Brief Summary

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

This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.

Related Clinical Trials

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

Phase II Study of Short-Term Cultured Anti-Tumor Autologous Lymphocytes After Lymphocyte-Depleting Chemotherapy in Metastatic Melanoma

NCT00513604

Melanoma Malignant Melanoma Melanoma, Experimental +1 more

COMPLETED PHASE2

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

NCT01005537

Melanoma (Skin)

NO_LONGER_AVAILABLE

Laboratory-Treated T Cells and Aldesleukin After Cyclophosphamide in Treating Patients With Stage IV Melanoma

NCT00553306

Recurrent Melanoma Stage IV Melanoma

COMPLETED PHASE1/PHASE2

Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Melanoma

NCT00003552

Stage IV Melanoma Recurrent Melanoma

TERMINATED PHASE1/PHASE2

Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

NCT01807182

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

COMPLETED PHASE2

Detailed Description

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

PRIMARY OBJECTIVES:

I. To assess the feasibility and safety of CXCR2 and NGFR transduced tumor-infiltrating lymphocytes (TIL) for treating metastatic malignant melanoma.

SECONDARY OBJECTIVES:

I. Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors.

II. Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL.

III. Characterize the clinical response and correlate with migration of CXCR2 transduced TIL to the tumor and levels of CXCL1 and CXCL8 at the tumor site.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).

After completion of study treatment, patients are followed up at weeks 6 and 12, every 3 months for a year, and then annually for up to 15 years.

Conditions

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

Metastatic Melanoma Stage III Cutaneous Melanoma AJCC v7 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 (genetically modified T-cells, high-dose aldesleukin

Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given IV

CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

NGFR-transduced Autologous T Lymphocytes

Intervention Type BIOLOGICAL

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Interventions

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

Aldesleukin

Given IV

Intervention Type BIOLOGICAL

CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes

Given IV

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

NGFR-transduced Autologous T Lymphocytes

Given IV

Intervention Type BIOLOGICAL

Quality-of-Life Assessment

Ancillary 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 CXCR2-transduced Autologous TILs (-)-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 Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 Quality of Life Assessment

Eligibility Criteria

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

Inclusion Criteria

* Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease (Turnstile I)
* Patients must have a lesion amenable to resection for the generation of TIL (Turnstile I)
* Patients must receive a magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) of the brain within 6 months of signing informed consent; if new lesions are present, patient must have definitive treatment; principal investigator (PI) or his designee should make final determination regarding enrollment (Turnstile I)
* Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 within 30 days of signing informed consent (Turnstile I)
* Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee
* Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP); a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (Turnstile I)
* Patients must have adequate TIL available (Turnstile II)
* Patients must have at least one biopsiable and measurable metastatic melanoma lesions \>= 1 cm (Turnstile II)
* Patients may have brain lesions which measure =\< 1 cm each (Turnstile II)
* Patients of both genders must practice birth control for four months after receiving the preparative regimen (lymphodepletion) and continue to practice birth control throughout the study; patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery (Turnstile II)
* Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is an acceptable form of birth control (Turnstile II)
* Pregnancy testing will be performed within 14 days prior to treatment (Turnstile II)
* Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (Turnstile II)
* Absolute neutrophil count greater than or equal to 1000/mm\^3 (Turnstile II)
* Platelet count greater than or equal to 100,000/mm\^3 (Turnstile II)
* Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II)
* Serum alanine transaminase (ALT) less than three times the upper limit of normal (Turnstile II)
* Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II)
* Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (Turnstile II)
* A stress cardiac test (stress thallium, stress multigated acquisition \[MUGA\] scan, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II)
* Forced expiratory volume in 1 second (FEV1) \> 65% of predicted within 6 months of lymphodepletion (Turnstile II) or
* Forced vital capacity (FVC) \> 65% of predicted within 6 months of lymphodepletion (Turnstile II)
* MRI/CT/PET of the brain within 30 days of lymphodepletion

Exclusion Criteria

* Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; PI or his designee shall make the final determination regarding appropriateness of enrollment (Turnstile I)
* Patients who are pregnant or nursing (Turnstile I)
* Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen (Turnstile II)
* Women who are pregnant will be excluded (Turnstile II)
* Any active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, such as abnormal stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease; PI or his designee shall make the final determination regarding appropriateness of enrollment (Turnstile II)
* Any form of primary or secondary immunodeficiency; must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (\> 500/mm\^3), white blood cell (WBC) (\> 3,000/mm\^3) or absence of opportunistic infections (Turnstile II)
* Requires no steroids within 4 weeks and have not used topical or inhalational steroids in the past 2 weeks prior to lymphodepletion; the exception being patients on chronic physiologic dose of steroid (Turnstile II)
* Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated (Turnstile II)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No