MelanomaPhase 2NCT01266603
High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI
A Phase 2 study testing HDIL-2 and recMAGE-A3 + AS15 in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- HDIL-2 and recMAGE-A3 + AS15
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2011to 1 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- STEP 1 Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
- Male or female patient with histologically proven, measurable unresectable or metastatic cutaneous melanoma
- Patient is >/= 18 years of age.
- Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for MAGE-A3 expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or liver lesion. Archival FFPE tumor tissue can be provided for the MAGE-A3 screening test, as long as the FFPE tumor tissue was obtained from a biopsy or resection and no systemic chemotherapy, immunotherapy or targeted therapy has been received by the patient between the tumor collection and the MAGE-A3 screening test. Fresh tumor tissue in RNAlater must be also available for gene signature testing. Patients must have at least one biopsiable cutaneous, subcutaneous, lymph node lesion, The tumor sample should be preferably from the same lesion as the FFPE tumor tissue. Cutaneous lesions must measure >/= 4mm and lymph nodes, subcutaneous, lung or liver lesions must measure >/= 1cm.
- STEP 2 ANA (antinuclear antibody) titer < 1:80
- STEP 2 The patient's tumor shows expression of MAGE-A3 gene.
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- ECOG performance status of 0 or 1.
- WBC >/= 3000/mm^3 and Hemoglobin >/= 9 g/dl
- Platelet count >/= 100,000/mm^3.
- Normal AST and ALT except for patients with liver metastases, in which serum ALT and AST </= 2.5 X upper limit of normal (ULN) will be permitted.
- Creatinine </= 1.5 mg/dL
- Normal total bilirubin except for patients with liver metastases, in which total bilirubin </= 1.5 X ULN will be permitted (patients with Gilbert's syndrome must have a total bilirubin less that 3.0 mg/dL).
- LDH </= 2 X ULN
- Stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) with estimated ejection fraction >50% within 6 months of signing consent form
- Pulmonary function tests showing FEV1 > 65% or FVC > 65% of predicted within 6 months of signing consent form
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception prior to treatment, throughout the study, and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. 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 post-menopausal. Post-menopause is defined as: Amenorrhea for 12 consecutive months without another cause, or For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 mIU/mL.
- (Continued #16) Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days before the start of treatment.
- Men must also agree to use an adequate method of contraception.
Who cannot join
- The patient has at any time received systemic chemotherapy, immunotherapy or targeted therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant setting, as long as this was performed at least 4 weeks before first study treatment administration).
- Brain metastasis or history of brain metastasis.
- Any types of melanoma other than cutaneous, i.e. ocular or mucosal .
- The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.
- Patients with a history of second malignancies are eligible provided that they have been free of recurrence from secondary malignancy for at least 3 years, does not include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.
- The patient has a history of an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis, and inflammatory bowel disease or an antinuclear antibody (ANA) titer > 1:80.
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- The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational compound.
- The patient has a family history of congenital or hereditary immunodeficiency.
- Known to be positive for viral hepatitis B or C (HBsAg or Anti HCV) or HIV (HIV antibodies) Patients should have a negative test within 6 months of starting treatment.
- Systemic steroid therapy, steroid-containing compounds or any other immunosuppressive agents or to be used for more than 7 consecutive days (at a dose of prednisone or equivalent of >/= 0.125 mg/kg/day).
- The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures. Each patient will be evaluated by the principal investigator or his designee.
- The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. Each patient will be evaluated by the principal investigator or his designee.
- Initiation of another anti-cancer therapy.
- For female patients: the patient is pregnant or lactating.
- WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase II Trial of High Dose Interleukin-2 (HDIL-2) With Recombinant MAGE-A3 Protein Combined With Adjuvant System AS15 (recMAGE-A3 + AS15) in Patients With Unresectable or Metastatic Melanoma
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- HDIL-2, recMAGE-A3 + AS15
- 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
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HDIL-2Drug
Also called Interleukin-2, IL-2, Aldesleukin, Proleukin
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 + AS15Biological
Also called Recombinant MAGE-A3 Protein, recMAGE-A3 + AS15 ASCI, MAGE-A3, MAGE-A3 ASCI
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.
| Study group | Role | What they receive |
|---|---|---|
| HDIL-2 + recMAGE-A3 + AS15 | Experimental | 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. Receives: Drug: HDIL-2; Biological: recMAGE-A3 + AS15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
To evaluate the objective response rate induced by the concurrent administration of HDIL-2 and recMAGE-A3 + AS15 ASCI in patients with MAGE-A3-positive, unresectable or metastatic melanoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Until disease progression or up to 3 years & 9 months
Secondary outcomes (2)
Rate of SAEs
To evaluate the safety and toxicity profile of HDIL-2 in combination with recMAGE-A3 + AS15 ASCI in participants with MAGE-A3-positive, unresectable or metastatic melanoma
Measured: Until treatment completed or up to 3 years & 9 months
Progression-free Survival
To evaluate the rate of stable disease, progression-free survival and the overall survival of patients with MAGE-A3- positive, unresectable or metastatic melanoma who received the combination of HDIL-2 and recMAGE-A3 + AS15 ASCI.
Measured: Until treatment completed or up to 3 years & 9 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study start22 Feb 2011
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Wen-Jen Hwu, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266603
- Sponsor's protocol ID
- 2010-0113
- Other IDs
- NCI-2011-00282
- Status last verified
- Feb 2020
- First submitted
- 20 Dec 2010
- Last updated
- 19 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
McQuade JL, Homsi J, Torres-Cabala CA, Bassett R, Popuri RM, James ML, Vence LM, Hwu WJ. A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma. BMC Cancer. 2018 Dec 19;18(1):1274. doi: 10.1186/s12885-018-5193-9.
PubMed 30567529
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of High Dose Interleukin-2 (HDIL-2) With Recombinant MAGE-A3 Protein Combined With Adjuvant System AS15 (recMAGE-A3 + AS15) in Patients With Unresectable or Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01266603
- Acronym / sponsor ID
- 2010-0113
- Conditions
- Melanoma
- Keywords
- Metastatic Melanoma, Unresectable Melanoma, HDIL-2, Interleukin-2, IL-2, Aldesleukin, Proleukin, recMAGE-A3 + AS15
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 22 Feb 2011 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Posted 19 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HDIL-2 + recMAGE-A3 + AS15 | Experimental | Drug: HDIL-2, Biological: recMAGE-A3 + AS15HDIL-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- STEP 1 Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
- Male or female patient with histologically proven, measurable unresectable or metastatic cutaneous melanoma
- Patient is >/= 18 years of age.
- Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for MAGE-A3 expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or liver lesion. Archival FFPE tumor tissue can be provided for the MAGE-A3 screening test, as long as the FFPE tumor tissue was obtained from a biopsy or resection and no systemic chemotherapy, immunotherapy or targeted therapy has been received by the patient between the tumor collection and the MAGE-A3 screening test. Fresh tumor tissue in RNAlater must be also available for gene signature testing. Patients must have at least one biopsiable cutaneous, subcutaneous, lymph node lesion, The tumor sample should be preferably from the same lesion as the FFPE tumor tissue. Cutaneous lesions must measure >/= 4mm and lymph nodes, subcutaneous, lung or liver lesions must measure >/= 1cm.
- STEP 2 ANA (antinuclear antibody) titer < 1:80
Key exclusion criteria (15 listed)
- The patient has at any time received systemic chemotherapy, immunotherapy or targeted therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant setting, as long as this was performed at least 4 weeks before first study treatment administration).
- Brain metastasis or history of brain metastasis.
- Any types of melanoma other than cutaneous, i.e. ocular or mucosal .
- The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.
- Patients with a history of second malignancies are eligible provided that they have been free of recurrence from secondary malignancy for at least 3 years, does not include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HDIL-2Also: Interleukin-2, IL-2, Aldesleukin, Proleukin720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle. | Drug | HDIL-2 + recMAGE-A3 + AS15 |
| recMAGE-A3 + AS15Also: Recombinant MAGE-A3 Protein, recMAGE-A3 + AS15 ASCI, MAGE-A3, MAGE-A3 ASCI300 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. | Biological | HDIL-2 + recMAGE-A3 + AS15 |
Primary outcome
Objective Response Rate
Time frame: Until disease progression or up to 3 years & 9 months
To evaluate the objective response rate induced by the concurrent administration of HDIL-2 and recMAGE-A3 + AS15 ASCI in patients with MAGE-A3-positive, unresectable or metastatic melanoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2 secondary outcomes
Rate of SAEs
Time frame: Until treatment completed or up to 3 years & 9 months
Progression-free Survival
Time frame: Until treatment completed or up to 3 years & 9 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30567529McQuade JL, Homsi J, Torres-Cabala CA, Bassett R, Popuri RM, James ML, Vence LM, Hwu WJ. A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma. BMC Cancer. 2018 Dec 19;18(1):1274. doi: 10.1186/s12885-018-5193-9.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Melanoma
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Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
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BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wen-Jen Hwu, MD,PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HDIL-2 and recMAGE-A3 + AS15 in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Until disease progression or up to 3 years & 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01266603, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2020.