Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Melanoma
Intervention: Cyclophosphamide (Drug); CD8+ T Cells (Procedure); Interleukin-2 (Drug); Ipilimumab (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Cassian Yee, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
Overall contact: Cassian Yee, MD, Phone: 713-792-2921
Summary
The goal of this clinical research study is to learn about the safety of giving CD8+T cells
with ipilimumab, cyclophosphamide, and IL-2 (aldesleukin). Researchers also want to learn
if this combination can help to control metastatic melanoma.
This study is divided into 2 parts: leukapheresis and treatment. In the leukapheresis
part, blood cells will be collected from you to be made into modified CD8+T cells and given
back to you in the treatment part.
CD8+T cells are a type of white blood cell. Researchers grow the T cells in the laboratory,
and they are designed to find melanoma cancer cells and may kill them.
Ipilimumab and aldesleukin are designed to increase the immune system's ability to fight
cancer.
Cyclophosphamide will be used at a very low dose to weaken the body's natural defense
against the T-cell transplant, so that the transplanted T-cells have a chance to grow and
multiply.
Clinical Details
Official title: Phase II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 for Patients With Metastatic Melanoma
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Overall Response
Detailed description:
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 5½ 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 5½ 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 1½
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 5½ 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 5½ 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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'.
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. Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic
imaging (X-ray, CT scan).
10. At least 4 Weeks must have elapsed since the last chemotherapy, radiotherapy or major
surgery. At least 6 Weeks for nitrosoureas, mitomycin C and liposomal doxorubicin. If
started before T-cell administration, ipilimumab infusions must be least 21 days
apart.
11. Toxicity related to prior therapy must either have returned to = grade 1, baseline,
or been deemed irreversible.
12. Evaluation of BRAFV600 mutation status.
13. Measurable tumor (by RECIST criteria).
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. Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam. Patients so identified will undergo pulmonary functions testing and
those with FEV1 < 2. 0 L or DLco (corr for Hgb) < 50% will be excluded.
4. Significant cardiovascular abnormalities as defined by any one of the following:
•Congestive heart failure, •Clinically significant hypotension, •Symptoms of coronary
artery disease, •Presence of cardiac arrhythmias on EKG requiring drug therapy
5. Active and untreated central nervous system (CNS) metastasis (including metastasis
identified during screening MRI or contrast CT).
6. 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.
7. 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.
8. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not
indicative of true active or chronic infection, the patient can be treated.
9. CBC and Chemistry profile prior to cyclophosphamide and T cell infusions: •WBC =
2000/uL •Hct = 24% or Hb ≤8 g/dL •ANC = 1000 •Platelets = 50,000 •Creatinine
>/= 3. 0 x ULN •AST/ALT >/= 2. 5 x ULN, •Bilirubin >/= 3 x ULN
10. Steroids are not permitted 3 days prior to T cell infusion and concurrently during
therapy.
11. Any non-oncology vaccine therapy used for the prevention of infectious disease within
1 month before or after any ipilimumab dose.
12. 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.
13. 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.
Locations and Contacts
Cassian Yee, MD, Phone: 713-792-2921
University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information
University of Texas MD Anderson Cancer Center Website
Starting date: January 2015
Last updated: June 23, 2015
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