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
Study Drug Administration:
If you were found to be eligible to take part in this study, you will begin to receive the
study drugs and other drugs that are given to help lower the risk of side effects.
The days leading up to Day 1 of the study are considered negative days. For example, the day
before Day 0 is Day -1.
On Days -7 and -6, you will receive cyclophosphamide each day by vein over about 2 hours.
On Day -7, you will receive mesna by vein non-stop over about 24 hours. This is help to
protect the bladder from side effects of cyclophosphamide.
On Days -5 to -1, you will receive fludarabine each day by vein over about 15-30 minutes.
On Day 0, you will receive CXCR2 and NGFR T-cells through a catheter over about 15-60
minutes. A catheter is a thin flexible tube that inserted into the body. The catheter may be
placed into a vein in your arm or in a large vein in your neck. If the cells need to be
given through a large vein either in your upper chest or in your neck, the area will be
numbed with medicine before the catheter is put in. Other catheters may be needed in one or
both of your arms to give you fluids, medicines, or extra nutrition. You will sign a
separate consent for the catheter, which will describe the procedure and the risks in more
On Days 1-5, you will receive aldesleukin by catheter over about 15 minutes every 8-16 hours
for up to 15 doses.
On Days 22-26, you will receive aldesleukin by catheter over about 15 minutes every 8-16
hours for up to 15 doses. You will only receive aldesleukin if your platelet counts are high
You will be given levofloxacin once a day by mouth or vein until your white blood cell count
rises. You will receive filgrastim through a needle under the skin once a day until your
white blood cell count rises. You will begin to receive fluconazole on Day 0 by mouth until
your white blood cell count rises. You will also take trimethoprim and sulfamethoxazole
(SMX) by mouth 2 times a day, beginning on Day -7 and continuing for at least 3 months after
chemotherapy. If you have herpes, you will receive acyclovir by mouth or valacyclovir by
vein if you are unable to take by mouth until your white blood cell count rises.
The drug furosemide will be given by vein while you receive cyclophosphamide to try to
increase the amount of urine your body makes.
The T-cell infusion may cause an allergic reaction such as fever, chills, and/or shivering.
You will take Tylenol (acetaminophen) by mouth before the T-cell infusion to decrease the
risk of these side effects.
You will receive the drug ondansetron by vein over 30 minutes to decrease the risk of
nausea and vomiting during chemotherapy.
It is possible that you will receive a 2nd round of chemotherapy, aldesleukin, and T-cells.
You will repeat the study visit schedule as well. Your doctor will discuss this with you.
Every 1-2 days during Days -7 to 26, blood (about 3 teaspoons) will be drawn for routine
While you receive CXCR2 and NGFR T-cells, your vital signs will be measured before T-cell
infusion, every 15 minutes during the infusion, and then 1 time an hour for 4 hours after
On Days 0, 6, and 27, blood (about 4 tablespoons) will be drawn to check the activity of the
T-cells and their ability to attack the tumor. If you return for follow up this blood will
also be drawn 6 weeks, 12 weeks, 3 months, 6 months, and 1 year after you receive the CXCR2
and NGFR T-cells.
On Days 6 and 27, you will have biopsies to check the status of the disease. The type of
biopsy will depend on the size and location of the tumor.
At about 6 and 12 weeks:
- You will have a physical exam.
- You will have a CT or PET/CT scan of the chest, abdomen, and pelvis to check the status
of the disease.
- You will have an MRI scan, CT scan, and/or a PET scan of the brain to check the status
of the disease.
You will return every 3-4 weeks for the first 2 months after treatment. Then every 1-3
months for the next 10 months. The study doctor will decide the types of tests that you
Length of Study:
You may receive up to 2 rounds of the study drugs (up to 12 weeks). You will no longer be
able to take the study drugs if the disease gets worse, if intolerable side effects occur,
or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-treatment
and follow-up visits.
If all of the tests are normal and show no change, blood (about 2-4 tablespoons) will be
collected from you at every visit and stored in case you develop symptoms later. This blood
may be tested to check the number of t-cells in your blood and how they are functioning. If
you give your consent below, in the optional procedures section, any blood left over from
these tests will be stored and used for use in future research.
Long Term Follow-Up:
One (1) time a year for 5 years after you receive the T-cells, you will have a physical
One (1) time a year for up to 15 years, you will be mailed a questionnaire about your health
and quality of life. This questionnaire should take about 15 minutes to complete. You will
be given a self-addressed, stamped envelope in order to return the questionnaire.
This is an investigational study. CXCR2 and NGFR T-cells is not FDA approved or
commercially available. It is currently being used for research purposes only.
Cyclophosphamide is FDA approved and commercially available for the treatment of several
types of cancer (such as leukemia, lymphoma, and breast cancer).
Fludarabine is FDA approved and commercially available for the treatment of B-cell chronic
Aldesleukin is FDA approved and commercially available for the treatment of Metastatic
melanoma or renal cell carcinoma.
Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity of CXCR2 Transduced Tumor Infiltrating Lymphocytes (TIL)
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.
Patrick Hwu, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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