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

NCT01740557 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 2009-0471NCI-2014-02655R01CA116206
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Immune-Related Response

  Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline. Response will be evaluated by positron emission tomography or computed tomography imaging.

  Up to 1 year

• Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities

  Possible grade 3 or worse toxicities not normally associated with lymphodepletion and high dose IL-2 will be reported.

  Up to 8 weeks

Secondary Outcomes (3)

• CXCR2 Transduction

  At infusion

• CXCL1 and CXCL8 Chemokines Produced

  At infusion

• 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.

  At infusion

Study Arms (1)

Treatment (genetically modified T-cells, high-dose aldesleukin

EXPERIMENTAL

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).

Biological: Aldesleukin; Biological: CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: NGFR-transduced Autologous T Lymphocytes; Other: Quality-of-Life Assessment

Interventions

Aldesleukin BIOLOGICAL

Given IV

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

Treatment (genetically modified T-cells, high-dose aldesleukin

CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes BIOLOGICAL

Given IV

Also known as: CXCR2-transduced Autologous TILs

Treatment (genetically modified T-cells, high-dose aldesleukin

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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (genetically modified T-cells, high-dose aldesleukin

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (genetically modified T-cells, high-dose aldesleukin

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (genetically modified T-cells, high-dose aldesleukin

NGFR-transduced Autologous T Lymphocytes BIOLOGICAL

Given IV

Treatment (genetically modified T-cells, high-dose aldesleukin

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (genetically modified T-cells, high-dose aldesleukin

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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)

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

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Cyclophosphamide; fludarabine phosphate

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

Results Point of Contact

• Title: Dr. Rodabe Amaria M.D.
• Organization: M D Anderson Cancer Center

rnamaria@mdanderson.org

(713) 792-2921

Study Officials

• Rodabe N Amaria

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 30, 2012
• First Posted: December 4, 2012
• Study Start: January 28, 2015
• Primary Completion: April 21, 2023
• Study Completion: April 21, 2023
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-09

Locations

US (1)