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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


Phase 1/Phase 2
14 Years
N/A
Not Enrolling
Both
Melanoma

Thank you

Trial Information

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
detail.

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
enough.

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.

Study Visits:

Every 1-2 days during Days -7 to 26, blood (about 3 teaspoons) will be drawn for routine
tests.

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
the infusion.

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
will have.

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
exam.

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
lymphocytic leukemia.

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.


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
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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity of CXCR2 Transduced Tumor Infiltrating Lymphocytes (TIL)

Outcome Description:

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.

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

Patrick Hwu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2009-0471

NCT ID:

NCT01740557

Start Date:

December 2013

Completion Date:

Related Keywords:

  • Melanoma
  • Melanoma
  • Metastatic Melanoma
  • Stage III in-transit, subcutaneous, or regional nodal disease
  • Cytoxan
  • Cyclophosphamide
  • Neosar
  • Mesna
  • Mesnex
  • Fludarabine
  • Fludarabine Phosphate
  • Fludara
  • IL-2
  • Interleukin-2
  • Aldesleukin
  • Proleukin
  • T-cells
  • Autologous tumor infiltrating lymphocytes
  • TIL
  • CXCR2
  • Melanoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030