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Trial record 14 of 40 for:    melanoma | Open Studies | interleukin-2

T-Cells Transduced With Either CXCR2 or Nerve Growth Factor Receptor (NGFR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by M.D. Anderson Cancer Center
Prometheus Laboratories
Key Biologics, LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: November 30, 2012
Last updated: January 29, 2015
Last verified: January 2015

The goal of this clinical research study is to learn the side effects of T-cells injected with CXCR2 and Nerve Growth Factor Receptor (NGFR) when given in combination with chemotherapy (cyclophosphamide and fludarabine) and aldesleukin to patients with metastatic melanoma in an attempt to allow them to better localize the tumor. The safety of this combination will also be studied.

Condition Intervention Phase
Drug: Cytoxan
Drug: Mesna
Drug: Fludarabine monophosphate
Procedure: T cell Infusion
Drug: IL-2
Other: Questionnaire
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Lymphodepletion Plus Adoptive Cell Transfer With T-Cells Transduced With CXCR2 and Nerve Growth Factor Receptor (NGFR) Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Toxicity of CXCR2 Transduced Tumor Infiltrating Lymphocytes (TIL) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

    Phase 1 Toxicity, defined as a grade 3 or 4 non-hematologic toxicity that cannot be resolved therapeutically within 2 weeks of onset, including nausea/vomiting, transaminitis, neutropenia with fever, and thrombocytopenia using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) 4.0 . Toxicities monitored daily basis beginning Day 0 (T-cell infusion) and continuing until discharged from hospital following the initial IL-2 infusion.

    Toxicity reporting: a.) Grade 2 or greater allergic reaction and b.) Grade 3 or 4 non-heme toxicities with the exception of: IL-2 expected toxicities; and Toxicities occurring within 24 hours post cell infusion that are reversible to grade 2 or less within 8 hours.

Secondary Outcome Measures:
  • Tumor Response using Immune-Related Response Criteria (irRC) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Tumor response defined following immune-related response criteria as 50% or greater decrease in tumor's linear dimension post treatment, compared to baseline using immune-related response criteria (irRC) which is a modified version of World Health Organization (WHO) criteria.

Estimated Enrollment: 36
Study Start Date: January 2015
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CXCR2 + NGFR T-cells
Cytoxan administered intravenously (IV) at 60 mg/kg/day over approximately 2 hours on Days -7 and -6. Mesna 60 mg/kg administered IV over 24 hours on Days -7 and -6. Fludarabine infused at 25 mg/m2 IV daily over approximately 15-30 minutes on Days -5 to -1. On day 0, all patients receive up to 1.5x10^11 T cells (including both CXCR2 and NGFR transduced TIL). TIL infused as an inpatient by IV over approximately 15-60 minutes. Twelve (12) to sixteen (16) hours after completing T cell infusion, all patients receive high dose interleukin-2 (IL-2) on an inpatient basis at standard dose of 720,000 IU/kg as an intravenous bolus over an approximate 15 minute period every 8-16 hours for up to 15 doses on Days 1 to 5, as tolerated.
Drug: Cytoxan
60 mg/kg/day by vein on Days -7 and -6.
Other Names:
  • Cyclophosphamide
  • Neosar
Drug: Mesna
60 mg/kg by vein on Days -7 and -6.
Other Name: Mesnex
Drug: Fludarabine monophosphate
25 mg/m2 by vein on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Procedure: T cell Infusion
Participants receive up to 1.5x10^11 T cells by vein (including both CXCR2 and NGFR transduced TIL) on Day 0.
Drug: IL-2
720,000 IU/kg by vein every 8-16 hours for up to 15 doses on Days 1 to 5.
Other Names:
  • Interleukin-2
  • Aldesldukin
  • Proleukin
Other: Questionnaire
Questionnaire completion about health and quality of life one (1) time a year for up to 15 years. Questionnaire should take about 15 minutes to complete.
Other Name: Survey

  Show Detailed Description


Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Turnstile I Inclusion Criteria - Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease. (Turnstile I)
  2. Patients must have a lesion amenable to resection for the generation of TIL. (Turnstile I)
  3. Patients must receive an MRI/CT/PET of the brain within 6 months of signing informed consent. If new lesions are present, patient must have definitive treatment. PI or his designee should make final determination regarding enrollment. (Turnstile I)
  4. Age greater than or equal to 18 years. (Turnstile I)
  5. Clinical performance status of ECOG 0 - 2 within 30 days of signing informed consent. (Turnstile I)
  6. 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
  7. 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)
  8. Chemotherapy/Cell Infusion Inclusion Criteria - Patients must have adequate TIL available (Turnstile II)
  9. Patients must have at least one biopsiable and measurable metastatic melanoma lesions >/= 1cm. (Turnstile II)
  10. Patients may have brain lesions which measure </= 1cm each (Turnstile II)
  11. 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)
  12. 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, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control (Turnstile II)
  13. Pregnancy testing will be performed within 14 days prior to treatment (Turnstile II)
  14. Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (Turnstile II)
  15. Absolute neutrophil count greater than or equal to 1000/mm^3 (Turnstile II)
  16. Platelet count greater than or equal to 100,000/mm^3 (Turnstile II)
  17. Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II)
  18. Serum ALT less than three times the upper limit of normal (Turnstile II)
  19. Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II)
  20. 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)
  21. A stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion. (Turnstile II)
  22. Pulmonary function tests (FEV1>65% or FVC>65%of predicted) within 6 months of lymphodepletion. (Turnstile II)
  23. MRI/CT/PET of the brain within 30 days of lymphodepletion

Exclusion Criteria:

  1. Turnstile I - 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)
  2. Patients who are pregnant or nursing (Turnstile I)
  3. Chemotherapy/Cell Infusion Exclusion Criteria - Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen. (Turnstile II)
  4. Women who are pregnant will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus (Turnstile II)
  5. 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)
  6. Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm3), WBC (> 3,000/mm3) or absence of opportunistic infections. (Turnstile II)
  7. 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)
  8. 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01740557

Contact: Patrick Hwu, MD 713-792-2921

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Prometheus Laboratories
Key Biologics, LLC
Principal Investigator: Patrick Hwu, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01740557     History of Changes
Other Study ID Numbers: 2009-0471, 2RO1CA116206-06, NCI-2014-02655
Study First Received: November 30, 2012
Last Updated: January 29, 2015
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:
Metastatic Melanoma
Stage III in-transit, subcutaneous, or regional nodal disease
Fludarabine Phosphate
Autologous tumor infiltrating lymphocytes

Additional relevant MeSH terms:
Nevi and Melanomas
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Fludarabine phosphate
Analgesics, Non-Narcotic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses processed this record on February 27, 2015