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

NCT01955460 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 2012-0758NCI-2014-01211RP110553-P4RM1012-012-1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies the side effects and best dose of genetically modified T-cells followed by aldesleukin in treating patients with stage III-IV melanoma. T-cells are a type of white blood cell that help the body fight infections. Genes that may help the T-cells recognize melanoma cells are placed into the T-cells in the laboratory. Adding these genes to the T cells may help them kill more tumor cells when they are put back in the body. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells.

Conditions

Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IIIA Cutaneous Melanoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• (Cohort A) Generation of TGF alpha (TGFa)-DNRII and NGFR transduced tumor infiltrating lymphocytes (TILs)

  Feasibility of generating TGFa-DNRII and NGFR transduced TILs and safety of treating patients with genetically modified T cells will be assessed. Feasibility will be defined as the production of virally transduced T cells and treatment of patients with these cells.

  Up to 5 years

• (Cohort B) The primary endpoint of growing enough TIL for patient treatment and sample size is 15 patients.

  The primary endpoint is feasibility (F) of growing enough TIL for patient treatment and sample size is 15 patients.) If you assume that Prob(F) follows 2s a non-informative beta (0.50, 0.50)prior, which has mean = 0.50 and effective sample size =1, then for example, if you observe 5/15 patients for whom F occurred and 10/15 for whom it did not, then a posterior 95% credible interval for Prob(F) would have lower and upper limits 0.14 to 0.58.

  Up to 6 months

Secondary Outcomes (4)

• (Cohort A) Response

  Up to 24 months

• (Cohort A) Number of DNRII transduced cells

  6 months

• (Cohort A) Number of NGFR transduced cells at infusion

  Day 0

• (Cohort A) Number of NGFR transduced cells based on tumor biopsy

  Up to 24 months

Study Arms (1)

Treatment (chemotherapy, autologous T-cell immunotherapy)

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 TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes 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; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: NGFR-transduced Autologous T Lymphocytes; Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes

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 (chemotherapy, autologous T-cell immunotherapy)

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 (chemotherapy, autologous T-cell immunotherapy)

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 (chemotherapy, autologous T-cell immunotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, autologous T-cell immunotherapy)

NGFR-transduced Autologous T Lymphocytes BIOLOGICAL

Given IV

Treatment (chemotherapy, autologous T-cell immunotherapy)

TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes BIOLOGICAL

Given IV

Also known as: TGFbDNRII-transduced Autologous TILs

Treatment (chemotherapy, autologous T-cell immunotherapy)

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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 or the collection of up to 5 needle core samples 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 (treatment naive) will be eligible (Turnstile I)
• Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability (Turnstile I)
• 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 (i.e. who has not had menses at any time in the preceding 12 consecutive months) (Turnstile I)
• Patients must have adequate TIL available (Turnstile II); pre-rapid expansion procedure (Pre-REP) TIL generated in the similar clinical trial 2004-0069 may also be utilized for Turnstile II
• Patients must have at least one biopsiable measurable metastatic melanoma, lesion \> or = to 1 cm (Turnstile II)
• Patients may have brain lesions =\< 1 cm each; the PI or designee will approve the treatment (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)
• Patients with negative pregnancy test (urine or serum) must be documented within 14 days of screening for WOCBP; a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not menses at any time in the preceding 12 consecutive months) (Turnstile II)
• Clinical performance status of ECOG 0-2 within 30 days of signing informed consent (Turnstile II)
• Absolute neutrophil count greater than or equal to 1000/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)
• Primary immunodeficiency and need for chronic steroid therapy, however prednisone is allowed at \< 10 mg/day (Turnstile I)
• Patients who are pregnant or nursing (Turnstile I)
• Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent (Turnstile I)
• Has had prior systemic cancer therapy within the past four weeks or v-raf murine sarcoma viral oncogene homolog B (B-RAF) or mitogen-activated protein kinase (MEK) inhibitors within 7 days at the time of the start of the lymphodepletion regimen (Turnstile II)
• Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus (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)
• Require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have 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)
• Patients who are solid organ transplant recipients
• Patients with prior bone marrow or stem cell transplantation

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

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

Study Officials

• Rodabe N Amaria

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Study Start: October 15, 2014
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)