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

This study is not yet open for participant recruitment.
Verified December 2013 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01740557
First received: November 30, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

The goal of this clinical research study is to learn the side effects of T-cells injected with CXCR2 and 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.

T cells are types of white blood cells that help your body fight infections. T-cells are designed to recognize and kill melanoma cells. Researcher want to grow your T-cells in a laboratory, inject them with CXCR2 and NGFR to be able to recognize tumor cells, and then give them back to you. This may help to control melanoma.

Cyclophosphamide is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.

Aldesleukin is designed to block the activity of cells that decrease the immune system's ability to fight cancer.


Condition Intervention Phase
Melanoma
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 ]
    Study will utilize National Cancer Institute Common Terminology Criteria (CTC) for Adverse Events version 4.0 for toxicity and Adverse Event reporting. Toxicity, immunologic effects and anti-tumor efficacy of cell infusions will be performed. Toxicities monitored and documented on a daily basis beginning at day 0 (T-cell infusion) and continuing until discharged from hospital following the initial IL-2 infusion. Maximum tolerated dose (MTD) defined as dose having posterior mean probability to toxicity closest to the targeted value .20.


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Primary clinical endpoint response defined following immune-related response criteria as 50% or greater decrease in tumor's linear dimension post treatment, compared to baseline. Immunological endpoints include (i) at infusion, Xc = number of CXCR2 transduced cells and Xs = number of NGFR transduced (control) cells, (ii) post treatment, based on tumor biopsy, Yc = number of CXCR2 transduced cells and Ys = number of NGFR transduced cells, and (iii) post treatment, ZCXCR2 = amount of CXCR2 cytokine and ZCXCR8 = amount of CXCL8 (IL-8) cytokine.


Estimated Enrollment: 36
Study Start Date: April 2014
Estimated Primary Completion Date: April 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

  Eligibility

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

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 14 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. 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. (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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01740557

Contacts
Contact: Patrick Hwu, MD 713-792-2921

Locations
United States, Texas
UT MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Patrick Hwu, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01740557     History of Changes
Other Study ID Numbers: 2009-0471
Study First Received: November 30, 2012
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
Metastatic Melanoma
Interleukin-2
Stage III in-transit, subcutaneous, or regional nodal disease
Cytoxan
Cyclophosphamide
Neosar
Mesna
Mesnex
Fludarabine
Fludarabine Phosphate
Fludara
IL-2
Aldesleukin
Proleukin
T-cells
Autologous tumor infiltrating lymphocytes
TIL
CXCR2

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Interleukin-2
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Mesna
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Mitogens
Vidarabine
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Mitosis Modulators
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on April 17, 2014