You will have a leukapheresis procedure to collect blood cells so they can be separated and
grown as CD8+T cells. For this procedure, you will need to stay seated in a chair and keep
both arms still for about 3 hours. Blood will be drawn from 1 arm, the white blood cells
will be separated from the rest of the blood cells in the leukapheresis machine, and the red
cells, platelets, and plasma (liquid part of the blood) will be returned through your other
arm.
The white blood cells will be collected into a sterile bag. A steady stream of blood will
flow from you into the leukapheresis machine and back into you through tubing attached to
the catheters and needles in your arms. Citrate will be added to the blood as it enters the
machine in order to lower the risk of your blood clotting in the machine.
If you cannot have a leukapheresis procedure, blood (about 2/3 cups each time) will be drawn
2-4 times to collect blood cells so they can be separated and grown as CD8+T cells.
Researchers may use the white blood cells that were previously collected from you when you
consented to take part in Protocol PA14-0138.
If enough white blood cells cannot be collected, you will not be enrolled in the study.
On the day of your leukapheresis visit:
- Blood (about 1 tablespoons) will be drawn for routine tests.
Once the T-cells collected during leukapheresis are modified in the laboratory and prepared
for your treatment, you will be screened again. You will be given a second consent form that
will describe this additional screening, as well as the study treatment.
There will be at least 3-4 months between the leukapheresis and the time when the CD8+T
cells are ready to give back to you. You may receive other therapies during this time as
long as you do not receive another treatment within 3 weeks before the CD8+T cell dose.
Please ask your doctor about your options during this 3-4 month period.
This is an investigational study. CD8+T cells are not FDA approved or commercially
available. They are currently being used for research purposes only.
Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at
MD Anderson.
Part 2 - Treatment:
Study Drug Administration:
If you agree to take part in this study, you will receive cyclophosphamide by vein over
about 30-60 minutes on Day -2 (2 days before you receive the CD8+ T cells). If the doctor
thinks it is needed, you will be given standard drugs to help decrease the risk of side
effects. You may ask the study staff for information about how the drug is given and its
risks.
On Day 0, you will receive the CD8+ T cells by vein over about 30-60 minutes. You will stay
in the hospital overnight after the dose.
Starting within 6 hours after the CD8+T cell infusion and then 2 times a day after that for
14 days, you will give aldesleukin as an injection into your skin around your abdomen. You
will be taught how to give yourself these injections.
On Days 1, 22, 43, and 64, you will receive ipilimumab by vein over about 90 minutes.
Study Visits:
On Day -2:
- You will have a physical exam.
- Blood (about 1 tablespoon) will be drawn for routine tests. This routine blood draw
will include a pregnancy test if you can become pregnant. To continue your
participation in this study, you cannot be pregnant.
On Days 0, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140:
- You will have a physical exam.
- Blood (about 5 tablespoons) will be drawn for routine tests, immune system tests, and
tests on how long the T-cells survive in your body.
- Between Day 35 and 42 and again between Day 77 and 84, you will have a CT scan to check
the status of the disease.
On Day 3, blood (about 5 tablespoons) will be drawn for routine tests, immune system tests,
and tests on how long the T-cells survive in your body.
If the doctor thinks it is needed to confirm the status of the disease, blood (about 1
tablespoons) will be drawn every 3-6 months for up to 3 years.
The study tests may be repeated or you may have additional tests performed anytime the
doctor thinks it is needed.
Some of the study tests may be done at your local clinic if you cannot return to MD
Anderson. The study staff will discuss this with you.
Length of Treatment:
The treatment portion of the study will last until Day 64. 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 after the follow-up.
End-of-Study Visit:
At Day 168:
- You will have a physical exam.
- Blood (about 5 tablespoons) will be drawn for routine tests, immune system tests, and
tests on how long the T-cells survive in your body.
Follow-Up:
Every 3 months after Day 84, unless the disease gets worse or you start another cancer
therapy, you will have a CT scan or x-rays to check the status of the disease. Every 3
months for up to 5 years, the study staff will call you or ask your doctor how you are
doing. If you are called, the calls should last about 10-15 minutes.
If the doctor thinks it is needed, you will return to the clinic every 4-6 weeks or as often
as the doctor thinks is needed. Blood (about 5 tablespoons) will be drawn for routine
tests, immune system tests, and tests on how long the T-cells survive in your body.
This is an investigational study. CD8+T cells are not FDA approved or commercially
available. They are currently being used for research purposes only. Cyclophosphamide,
ipilimumab, and aldesleukin are FDA approved and commercially available for the way they are
being used in this study.
Up to 30 participants will be enrolled in this multicenter study. Up to 20 will take part at
MD Anderson.
Inclusion Criteria:
1. Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic
disease.
2. Male or female subjects >/= 18 years of age.
3. Expression of HLA-A2.
4. ECOG/ Zubrod performance status of '0-1' at screening visit.
5. Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study in such a manner that the risk
of pregnancy is minimized. Suggested precautions should be used to minimize the risk
or pregnancy for at least 1 month before start of therapy, and while women are on
study for up to 3 months after T cell infusion, and at least 8 weeks after the study
drug is stopped. WOCBP include any female who has experienced menarche and who has
not undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation or bilateral oophorectomy) or is not postmenopausal.
6. Men must be willing and able to use an acceptable method of birth control, for at
least 3 months after completion of the study, if their sexual partners are WOCBP.
7. Willing and able to give informed consent.
8. Adequate venous access - consider PICC or central line.
9. Evaluation of BRAFV600 mutation status.
10. Measurable tumor (by RECIST criteria).
11. MART 1 or SLC45A2 (+) staining results. (If patients have not had staining test in
the past, the test will be run after patient consent is obtained, but before
enrollment).
Exclusion Criteria:
1. Any other malignancy from which the patient has been disease-free for less than 5
years, with the exception of adequately treated and cured basal or squamous cell skin
cancer, superficial bladder cancer, carcinoma in situ of the cervix.
2. Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception. Women of childbearing potential with a
positive pregnancy test within 3 days prior to entry.
3. Active and untreated central nervous system (CNS) metastasis (including metastasis
identified during screening MRI or contrast CT). No signs or symptoms of CNS mets
within the last 30 days (from enrollment evaluation). No single lesion larger than
1cm No more than 5 lesions
4. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are
excluded from this study, as are patients with a history of autoimmune disease (e.g.
Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible
progression during treatment would be considered by the Investigator to be
unacceptable.
5. Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events, such as a condition associated with frequent
diarrhea.
6. Positive screening tests for HIV, Hep B, and Hep C (referencing blood draw at
leukapheresis screening). If positive results are not indicative of true active or
chronic infection, the patient can be treated.
7. CBC and Chemistry profile prior to cyclophosphamide and T cell infusions: WBC </=
1000/uL Hct </= 24% or Hemoglobin </=8 g/dL ANC </= 500 Platelets </= 50,000
Creatinine >/= 3.0 x ULN AST/ALT >/= 2.5 x ULN, Bilirubin >/= 3 x ULN
8. Steroids are not permitted 3 days prior to T cell infusion and concurrently during
therapy.
9. Any non-oncology vaccine therapy used for the prevention of infectious disease within
1 month before or after any ipilimumab dose.
10. Patients may not be on any other treatments for their cancer aside from those
included in the protocol. Patients may not undergo another form of treatment
concurrently with this study.
11. Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception. Women of childbearing potential with a
positive pregnancy test within 3 days prior to entry.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
