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Ipilimumab With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Melanoma Mets Pts

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ClinicalTrials.gov Identifier: NCT01701674
Recruitment Status : Active, not recruiting
First Posted : October 5, 2012
Results First Posted : May 2, 2017
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
Iovance Biotherapeutics, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Melanoma
Interventions Drug: Ipilimumab
Procedure: Tumor Infiltrating Lymphocytes (TIL)
Drug: Administration of Lymphodepletion
Drug: Cyclophosphamide as Part of Lymphodepletion
Drug: Fludarabine as Part of Lymphodepletion
Drug: High Dose IL-2
Biological: Adoptive Cell Therapy with TIL
Enrollment 13
Recruitment Details Participants were enrolled at Moffitt Cancer Center, April 2013 through July 2014.
Pre-assignment Details  
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Period Title: Overall Study
Started 13
Completed 12
Not Completed 1
Reason Not Completed
Unable to safely complete treatment             1
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
All participants (13). All evaluable participants (12) may be referenced for some outcome measures.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
<=18 years
0
   0.0%
Between 18 and 65 years
10
  76.9%
>=65 years
3
  23.1%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 13 participants
49
(22 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
6
  46.2%
Male
7
  53.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 13 participants
13
 100.0%
1.Primary Outcome
Title Occurrence of Dose Limiting Toxicity (DLT) Events
Hide Description Occurrence of adverse events with dose limiting toxicity, per adverse event category.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description:
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: DLT events
Eye-related: Uveitis 1
Gastrointestinal: Colitis 1
2.Primary Outcome
Title Rate of Meeting Feasibility Requirements
Hide Description Number of participants who were successfully treated with at least 2 doses of ipilimumab and received TIL. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥ 6/10) of the patients with TIL.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description:
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
12
  92.3%
3.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description Overall Response: Complete Response (CR) + Partial Response (PR), per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by computed tomography (CT) scan. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions..
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants.
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description:
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: percentage of participants
38.5
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Progression-free survival (PFS) per RECIST V1.1, defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD): At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants.
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description:
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: months
7.4
(1.5 to 42)
Time Frame 3 years, 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Experimental: Combination Therapy
Hide Arm/Group Description The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
All-Cause Mortality
Experimental: Combination Therapy
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Experimental: Combination Therapy
Affected / at Risk (%) # Events
Total   9/13 (69.23%)    
Endocrine disorders   
Hypothyroidism * 1  1/13 (7.69%)  1
Eye disorders   
Uveitis * 1  1/13 (7.69%)  1
Gastrointestinal disorders   
Abdominal pain * 1  1/13 (7.69%)  1
Colonic perforation * 1  1/13 (7.69%)  1
Constipation * 1  1/13 (7.69%)  1
Diarrhea * 1  1/13 (7.69%)  1
Small intestinal obstruction * 1  1/13 (7.69%)  1
Immune system disorders   
Autoimmune disorder * 1  1/13 (7.69%)  1
Infections and infestations   
Abdominal infection * 1  1/13 (7.69%)  1
Appendicitis * 1  1/13 (7.69%)  1
Catheter related infection * 1  1/13 (7.69%)  1
Injury, poisoning and procedural complications   
Fracture * 1  1/13 (7.69%)  1
Vascular access complication * 1  1/13 (7.69%)  1
Investigations   
Investigations - Other, SIADH * 1  1/13 (7.69%)  1
Metabolism and nutrition disorders   
Dehydration * 1  2/13 (15.38%)  2
Hyponatremia * 1  1/13 (7.69%)  1
Musculoskeletal and connective tissue disorders   
Chest wall pain * 1  1/13 (7.69%)  1
Nervous system disorders   
Presyncope * 1  1/13 (7.69%)  1
Syncope * 1  1/13 (7.69%)  1
Psychiatric disorders   
Anxiety * 1  1/13 (7.69%)  1
Renal and urinary disorders   
Cystitis non-infective * 1  2/13 (15.38%)  2
Renal and urinary disorders - Other, Cistitis infective * 1  1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea * 1  2/13 (15.38%)  2
Vascular disorders   
Hypotension * 1  1/13 (7.69%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Experimental: Combination Therapy
Affected / at Risk (%) # Events
Total   13/13 (100.00%)    
Blood and lymphatic system disorders   
Anemia * 1  12/13 (92.31%)  82
Blood and lymphatic system disorders - Other * 1  1/13 (7.69%)  1
Febrile neutropenia * 1  10/13 (76.92%)  10
Cardiac disorders   
Atrial fibrillation * 1  1/13 (7.69%)  1
Cardiac disorders - Other * 1  3/13 (23.08%)  4
Palpitations * 1  1/13 (7.69%)  1
Sinus bradycardia * 1  1/13 (7.69%)  2
Sinus tachycardia * 1  9/13 (69.23%)  12
Ventricular tachycardia * 1  1/13 (7.69%)  1
Endocrine disorders   
Endocrine disorders - Other * 1  3/13 (23.08%)  4
Hypothyroidism * 1  1/13 (7.69%)  2
Eye disorders   
Blurred vision * 1  3/13 (23.08%)  3
Cataract * 1  1/13 (7.69%)  1
Conjunctivitis * 1  1/13 (7.69%)  1
Dry eye * 1  2/13 (15.38%)  2
Eye disorders - Other * 1  3/13 (23.08%)  4
Eye pain * 1  1/13 (7.69%)  1
Uveitis * 1  1/13 (7.69%)  2
Gastrointestinal disorders   
Abdominal pain * 1  5/13 (38.46%)  8
Bloating * 1  2/13 (15.38%)  2
Colitis * 1  2/13 (15.38%)  3
Constipation * 1  7/13 (53.85%)  10
Diarrhea * 1  11/13 (84.62%)  30
Dry mouth * 1  1/13 (7.69%)  1
Dysphagia * 1  1/13 (7.69%)  1
Gastroesophageal reflux disease * 1  2/13 (15.38%)  2
Gastrointestinal disorders - Other * 1  5/13 (38.46%)  6
Mucositis oral * 1  4/13 (30.77%)  6
Nausea * 1  13/13 (100.00%)  31
Vomiting * 1  9/13 (69.23%)  11
General disorders   
Chills * 1  10/13 (76.92%)  16
Edema limbs * 1  5/13 (38.46%)  8
Fatigue * 1  11/13 (84.62%)  33
Fever * 1  7/13 (53.85%)  12
Flu like symptoms * 1  3/13 (23.08%)  4
General disorders and administration site conditions - Other * 1  7/13 (53.85%)  15
Localized edema * 1  2/13 (15.38%)  2
Malaise * 1  1/13 (7.69%)  1
Non-cardiac chest pain * 1  2/13 (15.38%)  2
Pain * 1  7/13 (53.85%)  13
Immune system disorders   
Allergic reaction * 1  1/13 (7.69%)  1
Immune system disorders - Other * 1  2/13 (15.38%)  2
Infections and infestations   
Bronchial infection * 1  1/13 (7.69%)  1
Infections and infestations - Other * 1  5/13 (38.46%)  5
Mucosal infection * 1  1/13 (7.69%)  1
Penile infection * 1  1/13 (7.69%)  2
Upper respiratory infection * 1  3/13 (23.08%)  3
Urinary tract infection * 1  2/13 (15.38%)  2
Wound infection * 1  1/13 (7.69%)  1
Injury, poisoning and procedural complications   
Bruising * 1  2/13 (15.38%)  2
Fall * 1  1/13 (7.69%)  2
Injury, poisoning and procedural complications - Other * 1  1/13 (7.69%)  1
Vascular access complication * 1  1/13 (7.69%)  1
Wound dehiscence * 1  1/13 (7.69%)  1
Investigations   
Activated partial thromboplastin time prolonged * 1  3/13 (23.08%)  4
Alanine aminotransferase increased * 1  11/13 (84.62%)  24
Alkaline phosphatase increased * 1  9/13 (69.23%)  18
Aspartate aminotransferase increased * 1  12/13 (92.31%)  26
Blood bilirubin increased * 1  5/13 (38.46%)  11
Cardiac troponin T increased * 1  1/13 (7.69%)  1
CPK increased * 1  6/13 (46.15%)  9
Creatinine increased * 1  3/13 (23.08%)  5
INR increased * 1  1/13 (7.69%)  1
Investigations - Other * 1  2/13 (15.38%)  7
Lipase increased * 1  1/13 (7.69%)  1
Lymphocyte count decreased * 1  12/13 (92.31%)  45
Lymphocyte count increased * 1  2/13 (15.38%)  2
Neutrophil count decreased * 1  12/13 (92.31%)  32
Platelet count decreased * 1  12/13 (92.31%)  61
Serum amylase increased * 1  1/13 (7.69%)  1
Weight gain * 1  1/13 (7.69%)  4
White blood cell decreased * 1  12/13 (92.31%)  49
Metabolism and nutrition disorders   
Acidosis * 1  1/13 (7.69%)  1
Anorexia * 1  8/13 (61.54%)  10
Dehydration * 1  2/13 (15.38%)  2
Hypercalcemia * 1  1/13 (7.69%)  2
Hyperglycemia * 1  2/13 (15.38%)  9
Hyperkalemia * 1  4/13 (30.77%)  7
Hypermagnesemia * 1  1/13 (7.69%)  1
Hypoalbuminemia * 1  12/13 (92.31%)  37
Hypocalcemia * 1  3/13 (23.08%)  8
Hypokalemia * 1  3/13 (23.08%)  3
Hypomagnesemia * 1  4/13 (30.77%)  7
Hyponatremia * 1  10/13 (76.92%)  32
Hypophosphatemia * 1  12/13 (92.31%)  21
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  3/13 (23.08%)  4
Arthritis * 1  1/13 (7.69%)  3
Bone pain * 1  1/13 (7.69%)  1
Generalized muscle weakness * 1  1/13 (7.69%)  1
Myalgia * 1  2/13 (15.38%)  2
Myositis * 1  2/13 (15.38%)  2
Pain in extremity * 1  5/13 (38.46%)  6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other * 1  2/13 (15.38%)  2
Tumor pain * 1  3/13 (23.08%)  4
Nervous system disorders   
Dizziness * 1  7/13 (53.85%)  10
Dysarthria * 1  1/13 (7.69%)  1
Dysgeusia * 1  2/13 (15.38%)  2
Headache * 1  10/13 (76.92%)  12
Nervous system disorders - Other * 1  1/13 (7.69%)  1
Paresthesia * 1  3/13 (23.08%)  3
Peripheral sensory neuropathy * 1  1/13 (7.69%)  1
Somnolence * 1  1/13 (7.69%)  1
Syncope * 1  1/13 (7.69%)  1
Psychiatric disorders   
Agitation * 1  1/13 (7.69%)  1
Anxiety * 1  1/13 (7.69%)  1
Depression * 1  1/13 (7.69%)  1
Insomnia * 1  3/13 (23.08%)  4
Renal and urinary disorders   
Acute kidney injury * 1  1/13 (7.69%)  2
Bladder spasm * 1  1/13 (7.69%)  2
Cystitis non-infective * 1  1/13 (7.69%)  1
Hematuria * 1  2/13 (15.38%)  2
Renal and urinary disorders - Other * 1  1/13 (7.69%)  4
Urinary frequency * 1  1/13 (7.69%)  1
Urinary tract pain * 1  1/13 (7.69%)  2
Urine discoloration * 1  1/13 (7.69%)  1
Reproductive system and breast disorders   
Erectile dysfunction * 1  1/13 (7.69%)  1
Scrotal pain * 1  1/13 (7.69%)  3
Vaginal discharge * 1  1/13 (7.69%)  1
Vaginal hemorrhage * 1  1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis * 1  2/13 (15.38%)  3
Bronchospasm * 1  1/13 (7.69%)  1
Cough * 1  8/13 (61.54%)  12
Dyspnea * 1  10/13 (76.92%)  18
Epistaxis * 1  2/13 (15.38%)  2
Hiccups * 1  2/13 (15.38%)  2
Hypoxia * 1  3/13 (23.08%)  3
Nasal congestion * 1  2/13 (15.38%)  2
Postnasal drip * 1  1/13 (7.69%)  1
Productive cough * 1  2/13 (15.38%)  3
Pulmonary edema * 1  5/13 (38.46%)  7
Respiratory, thoracic and mediastinal disorders - Other * 1  4/13 (30.77%)  4
Sore throat * 1  3/13 (23.08%)  4
Skin and subcutaneous tissue disorders   
Alopecia * 1  5/13 (38.46%)  7
Dry skin * 1  3/13 (23.08%)  3
Erythema multiforme * 1  2/13 (15.38%)  3
Pruritus * 1  8/13 (61.54%)  18
Rash acneiform * 1  1/13 (7.69%)  1
Rash maculo-papular * 1  8/13 (61.54%)  22
Skin and subcutaneous tissue disorders - Other * 1  7/13 (53.85%)  9
Surgical and medical procedures   
Surgical and medical procedures - Other * 1  2/13 (15.38%)  2
Vascular disorders   
Capillary leak syndrome * 1  4/13 (30.77%)  4
Flushing * 1  1/13 (7.69%)  1
Hot flashes * 1  1/13 (7.69%)  1
Hypertension * 1  1/13 (7.69%)  2
Hypotension * 1  9/13 (69.23%)  14
Lymphedema * 1  3/13 (23.08%)  3
Vascular disorders - Other * 1  1/13 (7.69%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Amod Sarnaik
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-8581
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01701674     History of Changes
Other Study ID Numbers: MCC-17057
CA184-213 ( Other Identifier: Bristol-Myers Squibb )
First Submitted: October 3, 2012
First Posted: October 5, 2012
Results First Submitted: March 22, 2017
Results First Posted: May 2, 2017
Last Update Posted: March 19, 2019