Trial Outcomes & Findings for Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity (NCT NCT01323517)
NCT ID: NCT01323517
Last Updated: 2018-05-15
Results Overview
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
1 year
Results posted on
2018-05-15
Participant Flow
Participant milestones
| Measure |
Ipilimumab, Melphalan and Dactinomycin
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity
Baseline characteristics by cohort
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 Participants
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearProgression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 Participants
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
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|---|---|
|
Progression Free Survival at One Year.
|
58 percentage of participants PFS at 1 year
|
SECONDARY outcome
Timeframe: 2 yearsOutcome measures
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 Participants
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
|
Toxicity of Additional Ipilimumab Will be Evaluated for All Treated Patients Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
|
26 Participants
|
SECONDARY outcome
Timeframe: 2 yearsProgression free survival, from time of ILI, will be determined by measuring the index lesions, non-index lesions, and new lesions as described below. Patients with deep lesions will have repeat CT Scan evaluation to quantitate the lesions. 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
Outcome measures
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=24 Participants
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
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|---|---|
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To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).
Complete Response
|
16 Participants
|
|
To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).
Partial Response
|
5 Participants
|
|
To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).
Stable Disease
|
1 Participants
|
|
To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).
Progressive Disease
|
2 Participants
|
SECONDARY outcome
Timeframe: 2 yearsSummaries of antibody response, comparison of pretreatment with post-ipilimumab and end of treatment will be assessed for percent of CD4, CD8, and CD68 positive cells
Outcome measures
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 Participants
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Pretreatment CD4
|
3 percent of positive cells
Interval 1.0 to 17.0
|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Posttreatment CD4
|
28 percent of positive cells
Interval 2.0 to 49.0
|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Pretreatment CD8
|
2 percent of positive cells
Interval 1.0 to 5.0
|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Posttreatment CD8
|
7 percent of positive cells
Interval 1.0 to 26.0
|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Pretreatment CD68
|
10 percent of positive cells
Interval 1.0 to 19.0
|
|
To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.
Posttreatment CD68
|
18 percent of positive cells
Interval 2.0 to 38.0
|
Adverse Events
Ipilimumab, Melphalan and Dactinomycin
Serious events: 10 serious events
Other events: 26 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 participants at risk
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
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Cardiac disorders
Acute coronary syndrome
|
3.8%
1/26 • 2 years
|
|
Renal and urinary disorders
Acute kidney injury
|
3.8%
1/26 • 2 years
|
|
Cardiac disorders
Atrial fibrillation
|
3.8%
1/26 • 2 years
|
|
Gastrointestinal disorders
Colitis
|
3.8%
1/26 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
11.5%
3/26 • 2 years
|
|
Vascular disorders
Hypotension
|
3.8%
1/26 • 2 years
|
|
Infections and infestations
Infections and infestations - Other, specify
|
3.8%
1/26 • 2 years
|
|
Infections and infestations
Lung infection
|
7.7%
2/26 • 2 years
|
|
General disorders
Malaise
|
3.8%
1/26 • 2 years
|
|
Cardiac disorders
Myocardial infarction
|
3.8%
1/26 • 2 years
|
|
General disorders
Non-cardiac chest pain
|
3.8%
1/26 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
3.8%
1/26 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic & mediastinal disorder Other, spec
|
3.8%
1/26 • 2 years
|
|
Gastrointestinal disorders
Retroperitoneal hemorrhage
|
7.7%
2/26 • 2 years
|
|
Infections and infestations
Sepsis
|
3.8%
1/26 • 2 years
|
|
Cardiac disorders
Supraventricular tachycardia
|
3.8%
1/26 • 2 years
|
|
Vascular disorders
Thromboembolic event
|
15.4%
4/26 • 2 years
|
Other adverse events
| Measure |
Ipilimumab, Melphalan and Dactinomycin
n=26 participants at risk
Ipilimumab, Melphalan and Dactinomycin: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
|
|---|---|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
7.7%
2/26 • 2 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
7.7%
2/26 • 2 years
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
7.7%
2/26 • 2 years
|
|
Infections and infestations
Urinary tract infection
|
7.7%
2/26 • 2 years
|
|
Gastrointestinal disorders
Stomach pain
|
7.7%
2/26 • 2 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
57.7%
15/26 • 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
46.2%
12/26 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
42.3%
11/26 • 2 years
|
|
Investigations
CPK increased
|
30.8%
8/26 • 2 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
26.9%
7/26 • 2 years
|
|
Infections and infestations
Papulopustular rash
|
23.1%
6/26 • 2 years
|
|
Endocrine disorders
Adrenal insufficiency
|
23.1%
6/26 • 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
19.2%
5/26 • 2 years
|
|
Investigations
Alanine aminotransferase increased
|
19.2%
5/26 • 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
15.4%
4/26 • 2 years
|
|
General disorders
Fatigue
|
15.4%
4/26 • 2 years
|
|
Endocrine disorders
Hypothyroidism
|
15.4%
4/26 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
15.4%
4/26 • 2 years
|
|
Investigations
Lymphocyte count decreased
|
11.5%
3/26 • 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.5%
3/26 • 2 years
|
|
Investigations
Blood bilirubin increased
|
11.5%
3/26 • 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
11.5%
3/26 • 2 years
|
|
Infections and infestations
Sinusitis
|
7.7%
2/26 • 2 years
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
2/26 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.7%
2/26 • 2 years
|
|
Gastrointestinal disorders
Colitis
|
7.7%
2/26 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
7.7%
2/26 • 2 years
|
|
General disorders
Pain
|
7.7%
2/26 • 2 years
|
Additional Information
Dr. Charlotte Ariyan, MD
Memorial Sloan Kettering Cancer Center
Phone: 212-639-6280
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place