IPI-Biotherapy for Patients With Metastatic Melanoma Previously Treated With Cytotoxic Drugs
18 Years
65 Years
Both
Melanoma
Trial Information
IPI-Biotherapy for Patients With Metastatic Melanoma Previously Treated With Cytotoxic Drugs
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 5 groups of 3-6 participants will be
enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in
Phase II.
If you are enrolled in the Phase I portion, the dose of ipilimumab you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of ipilimumab. Each new group will receive a higher dose of ipilimumab than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of ipilimumab is found.
If you are enrolled in the Phase II portion, you will receive ipilimumab at the highest dose
that was tolerated in the Phase I portion.
All participants will receive the same dose level of interferon alfa-2b and aldesleukin.
Study Drug Administration:
The study drugs will be given in 3 stages: induction, consolidation, and maintenance.
Induction:
Induction will last 12 weeks. You will receive the study drugs in up to four 3-week cycles:
- You will receive ipilimumab by vein over 90 minutes on Day 1 of each cycle.
- You will receive aldesleukin in the hospital by vein as a continuous infusion on Days
2-5 of each cycle.
- You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each
cycle.
Consolidation:
Consolidation will last 12 weeks. You will receive the study drugs in up to four 3-week
cycles:
- You will receive ipilimumab by vein over 90 minutes on Day 1 of Cycle 1.
- You will receive aldesleukin in the hospital by vein as a continuous infusion on Days
2-5 of each cycle.
- You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each
cycle.
Maintenance:
Maintenance will last about 1½ years. You will receive ipilimumab by vein over 90 minutes
on Day 1 of up to six 12-week cycles.
Other Drugs:
You will be given other drugs to help lower the risk of side effects. The study staff will
tell you about these drugs, how they will be given, and the possible risks.
Study Visits:
Before each cycle (+/- 3 days):
- You will be asked about any drugs you may be taking and any side effects you may have
had.
- Your performance status will be recorded.
- Your vital signs will be measured.
- Blood (about 1 teaspoon) will be drawn for routine tests and tests of your liver and
kidney function.
- If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
pregnancy test.
Every week, blood (about 1 teaspoon) will be drawn for routine tests.
At the end of each cycle, you will have a physical exam, including measurement of your
weight. Any tumor that can be felt with the hands will be measured during the physical exam
to see if it has changed size.
Every 2 cycles (+/- 7 days), you will have a chest x-ray and CT or MRI scans to check the
status of the disease.
Anytime the doctor thinks it is needed, photos of the skin lesions will be taken. Your
private areas will be covered (as much as possible), and a picture of your face will not be
taken unless there are lesions on your face.
Length of Study:
You may continue taking the study drugs for up to 2 years. 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
visit and follow-up.
End-of-Treatment Visit:
Within 14 days after you stop the study therapy, the following tests and procedures will be
performed:
- You will have a physical exam, including measurement of your vital signs and weight.
- Your performance status will be recorded.
- You will be asked about any drugs you may be taking and any side effects you may have
had.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have a CT or MRI scan.
Every 2 months for up to 3 years, you will also be contacted by phone or during a clinic
visit to see how you are doing.
This is an investigational study. Ipilimumab, interferon alfa-2b, and aldesleukin are FDA
approved and commercially available to treat melanoma. Giving these drugs in combination is
investigational.
Up to 88 patients will take part in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Patients with histologically documented diagnosis of advanced stage IV or
unresectable stage III melanoma are eligible.
2. They should have recurrent melanoma with measurable or evaluable sites of disease,
1.0 cm or larger, in order to assess the response to treatment by the immune-related
response criteria (irRC).
3. Phase I: Patients with prior therapy who do not have alternative treatment of higher
priority will be eligible. Phase II: the patient may have been treated with cytotoxic
drugs or targeted therapies but not with IL-2, interferon and anti-CTLA4 drugs for
metastatic disease. Adjuvant ipilimumab will not be permitted. Only adjuvant
interferon will be permitted. Prior radiation therapy for metastatic melanoma is
permitted provided the patient has unirradiated metastatic sites for response
evaluation and has fully recovered from its toxicity.
4. Patients between 18 years of age and 65 years of age with an ECOG performance status
of 0, 1 or 2 will be eligible.
5. They should have normal blood counts with a white blood count (WBC) count of more
than or equal to 3000/mm^3 an absolute neutrophil count of more than or equal to
1500/mm^3 and a platelet count of more than 100,000/mm^3 and have no impairment of
renal function (serum creatinine less than 1.1 mg/dl for females and less than 1.4
mg/dl for males), hepatic function (serum bilirubin level of less than 1.2 mg/dl) and
no evidence of significant cardiac or pulmonary dysfunction.
6. They should have no significant intercurrent illness such as an active infection
associated with fever lasting more than 24 hours requiring antibiotics, uncontrolled
psychiatric illness, hypercalcemia (calcium greater than 11 mg), or active
gastrointestinal (GI) bleeding.
7. Females of child-bearing potential (non-childbearing is defined as greater than one
year post-menopausal or surgically sterilized) must use acceptable contraceptive
methods( abstinence, intrauterine device, oral contraceptive or double barrier
devices) and must have a negative serum or urine pregnancy test within 14 days prior
to beginning treatment on this trial. Sexually active men must also use acceptable
contraceptive methods for the duration of time on study.
Exclusion Criteria:
1. Patients with bone metastases only.
2. Patients with brain metastases unless all of their metastatic brain lesions have been
resected or treated with stereotactic radiotherapy with gamma rays and they are off
corticosteroids. Patient should not have significant brain edema. Patients with
spinal cord compression and leptomeningeal disease. No major surgery or radiation
therapy within 21 days before starting treatment.
3. Patients with significant cardiac illness such as symptomatic coronary artery disease
or previous history of myocardial infarction, impaired left ventricle function
(Ejection Fraction less than 50%) on account of any organic disease such as
hypertension or valvular heart disease or serious cardiac arrhythmia requiring
therapy. Patients will be evaluated by the investigator or his designee.
4. Patients with significant impairment of pulmonary function on account of chronic
bronchitis or chronic obstructive pulmonary disease (COPD) which has resulted in
impairment of vital capacity of FEV1 to less than 65% of predicted normal values.
5. Patients with symptomatic effusions on account of pleural, pericardial or peritoneal
metastases of melanoma.
6. Patients who are unable to return for follow-up visits as required by this study.
7. Patients with a history of second malignant tumor, other than the common skin cancers
- basal and squamous carcinomas, within the past 3 years and uncertainty about the
histological nature of the metastatic lesions. Cases with other types of malignancies
should be reviewed and decided by the Principal Investigator (PI) of the study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression Free survival (PFS)
Outcome Description:
Progression-free survival determined from the start of the study until disease progression or death, whichever is first and estimated using the method of Kaplan-Meier.
Outcome Time Frame:
Assessed at 6-months then until disease progression or death.
Safety Issue:
No
Principal Investigator
Agop Y. Bedikian, MD,BS
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2011-0074
NCT ID:
NCT01409187
Start Date:
October 2011
Completion Date:
Related Keywords:
- Melanoma
- Melanoma
- Metastatic Melanoma
- Cytotoxic Drugs
- IPI-Biotherapy
- Ipilimumab
- Yervoy
- BMS-734016
- MDX010
- Interferon
- IFN Alpha-2b
- Intron A
- Interferon Apha-2b
- Interleukin-2
- IL-2
- Aldesleukin
- Proleukin
- Melanoma
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