Conditions: Melanoma
Keywords: Metastatic Melanoma Unresectable Melanoma HDIL-2 Interleukin-2 IL-2 Aldesleukin Proleukin recMAGE-A3 + AS15 ASCI recMAGE-A3 Recombinant MAGE-A3 protein recMAGE-A3 + AS15 ASCI MAGE-A3 MAGE-A3 ASCI
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 44
Healthy volunteers: no

Brief summary:
The goal of this clinical research study is to learn if high-dose interleukin-2 (HDIL-2), when given in combination with recMAGE-A3 + AS15 ASCI (Antigen-Specific Cancer Immunotherapeutic), can help to control unresectable or metastatic melanoma in patients whose tumor tissue has the MAGE-A3 protein. The safety of this drug combination will also be studied. Researchers will also use samples of the original tumor or metastatic tissue (for example, lymph nodes or liver or lung) that are collected during screening to study if response to the study drug is related to the genes in the tissue.

Detailed description:
The Study Drugs:

HDIL-2 is similar to a hormone naturally found in the body that boosts the immune system by helping "natural killer" (NK) cells live longer and work better. NK cells are a type of white blood cell that kill other cells, and they may kill cancer cells.

ASCI is a immunotherapy designed to teach your immune system to fight cancer in the same way that you are given vaccines to prevent disease by teaching your immune system to fight an infection caused by germs. Because the cancer is made by your own body, the immune system does not recognize the cancer cells as being harmful. Your immune system needs to be "trained" to recognize the cancer cells. This is done by injecting a protein (the MAGE-A3 protein) that is found in the tumor and training your body to recognize it and to destroy the cells that have this protein. This may increase the effectiveness of IL-2 by slowing the growth of the cancer cells, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin the study drugs within 14 days of signing the second consent form. To receive the study drugs, you will be admitted to the hospital, either in the intensive care unit (ICU) or a specifically designated nursing unit where study drugs can be administered, on Day 2 of each cycle and may remain in the hospital for up to 7 days each cycle.

You may receive a total of 24 ASCI doses either in combination with HDIL-2 or alone. You may receive the study drugs in combination for up to 30 weeks. After that, you may receive the ASCI study medication alone for up to 157 more weeks.

Cycle 1 is 14 days (Weeks 1 and 2):

* On Day 1 of Cycle 1, you will receive the ASCI study medication as an injection. Each injection will be given in the muscle of your upper arm or in your thigh. You will be watched in the clinic for at least 30 minutes after each injection.
* On Day 2 (+/- 2 business days), you will receive HDIL-2 through a catheter (a small plastic tube that is put into your vein under your collar bone or in your arm) over 15 minutes. HDIL-2 treatment will be delayed in cycles 2, 3, 4, 5, 6, 7, or 8 until all HDIL-2 related side effects either go away or the study doctor thinks they are under control.

Cycle 2 is 42 days (Weeks 3-8):

* On Day 1 of Weeks 3, 5, and 7 (+/- 2 business days) , you will receive the ASCI study medication as an injection.
* On Day 2 of Week 3 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 3 is 14 days (Weeks 9 and 10):

* On Day 1 of Week 9 (+/- 2 business days), you will receive the ASCI study medication as an injection.
* On Day 2 of Week 9 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 4 is 49 days (Weeks 11-17):

* On Day 1 of Weeks 11 and 15 (+/- 2 business days), you will receive the ASCI study medication as an injection.
* On Day 2 of Week 11 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 5 is 21 days (Weeks 18-20):

* On Day 1 of Week 18 (+/- 2 business days), you will receive the ASCI study medication an injection.
* On Day 2 of Week 18 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 6 is 42 days (Weeks 21-26):

* On Day 1 of Weeks 18, 21, and 24 (+/- 2 business days), you will receive the ASCI study medication as an injection.
* On Day 2 of Weeks 18 and 21 (+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 7 is 21 days (Weeks 27-29):

* On Day 1 of Week 27 (+/- 2 business days), you will receive the ASCI study medication as an injection.
* On Day 2 of Week 27(+/- 2 business days), you will receive HDIL-2 by vein.

Cycle 8 is 28 days (Weeks 30-33):

* On Day 1 of Week 30 (+/- 2 business days), you will receive the ASCI study medication as an injection.
* On Day 2 of Week 30 (+/- 2 business days), you will receive HDIL-2 by vein.

On Day 1 of Weeks 34, 40, 46, 52, 64, 76, 88, and 100 (+/- 2 business days), you will receive the ASCI study medication as an injection.

Study Visits:

On Day 1 of Weeks 1, 3, 5, 7, 9, 11, 15, 18, 21, 24, 27, and 30 (+/- 2 business days):

* You will have a physical exam, including measurement of your weight and vital signs. °Blood (about 2 tablespoons) will be drawn for routine tests.
* You will be asked about any side effects you may be having and drugs you are taking.

On Day 2 of Weeks 1, 3, 5, 7, 9, 11, 18, 21, 27, and 30 (+/- 2 business days):

* Blood (about 2 tablespoons) will be drawn for routine tests.
* You will be asked about any side effects you may be having and drugs you are taking.

During Weeks 8, 17, 26, 33, 39, 51, 63, 75, 87, 99, 123, 147, 171, and 195 (+/- 1 week):

* You will have and a CT scan of your chest, abdomen, and pelvis to check the status of the disease.
* You will also have an MRI scan or CT scan of the brain to check the status of the disease.
* You will have photographs of your lesions taken if indicated by your doctor.

On Day 1 of Weeks 34, 40, 46, 52, 64, 76, 88, 100, 124, 148, 172, and 196 (+/- 2 business days):

* You will have a physical exam, including measurement of your weight and vital signs.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* You will be asked about any side effects you may be having and drugs you are taking.

Additional Blood Draws:

Additional blood (about 4 tablespoons each time) will be drawn for laboratory tests to look at how the study drug combination may affect the immune system. These blood draws will be collected on Day 1 of cycle 1 and again during cycle 1 48 hours after the last dose of IL-2. Additional blood draws (about 4 tablespoons each time) will also Part of the blood drawn for these tests will be sent to GSK Biologicals (or a contracted laboratory) for testing.

Length of Study:

You may continue to receive the study drug combination for up to 8 cycles (33 weeks) and ASCI alone for up to 76 more weeks (+/- 2 business days). If you continue beyond completing 8 cycles of HDIL-2, you will receive the ASCI on Day 1 (+/- 2 business days) every 6 weeks for 4 doses (weeks 34, 50, 46, and 52), then on Day 1 (+/- 2 business days) every 12 weeks (weeks 64, 76, 98, and 110) for 4 doses, then on Day 1 (+/- 2 business days) of every 24 weeks (Weeks 134, 158, 182, and 187) for 4 doses.

You will be taken off the study therapy early if the disease gets worse, you experience intolerable side effects, or the study doctor thinks it is in your best interest. If you are removed from the study because of intolerable side effects, you will be followed weekly by either a phone call or clinic visit until the side effect is tolerable.

End-of-Dosing Visit:

After receiving the last dose of study drug combination, you will have an end-of-dosing visit:

* Your medical history will be reviewed and you will be asked about any side effects you may be having and drugs you are taking.
* You will have a physical exam, including measurement of your weight and vital signs.
* Blood (about 3 tablespoons) will be drawn for routine tests and ANA testing.

Follow-Up Visits:

You will have follow-up visits after your last dose of study drug, if the disease does not get any worse. Starting after the last dose of study drug, you will have 1 visit every 3 months for the 1st year, every 4 months for the 2nd year, every 6 months for the 3rd and 4th year, then once a year for up to 10 years (+/- 2 business days). At these visits, the following will be performed:

* You will have a physical exam, including measurement of your weight and vital signs.
* If the study doctor thinks it is needed, blood (about 2 tablespoons) will be drawn for routine tests.
* If the study doctor thinks it is needed, you will have a chest x-ray, CT scan of your chest, abdomen, and pelvis, and/or MRI scan or CT scan of the brain to check the status of the disease.

If the disease begins to get worse, information about the status of your health will be collected every 2 months. If you are not able to come into the clinic to complete this visit, you will be asked for this information over the phone. The phone call should last about 10-15 minutes each time.

This is an investigational study. IL-2 is commercially available and FDA approved for the treatment of metastatic melanoma. HDIL-2 is a higher dose than the standard approved dose of IL-2. The ASCI study medication is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Arms:
arm 1: HDIL-2 720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. recMAGE-A3 300 μg plus 420 μg of CpG7909 (a part of the Adjuvant System AS15) by intermuscular injection within 24 hours from first dose of HDIL-2.

Interventions: intervention 1: HDIL-2 intervention 2: recMAGE-A3 + AS15
Intervention descriptions: intervention 1: 720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. intervention 2: 300 μg plus 420 μg of CpG7909 (a part of the Adjuvant System AS15) by intermuscular injection within 24 hours from first dose of HDIL-2.

Protocol document:
Prot_SAP_000.pdf: