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Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01005745
Recruitment Status : Active, not recruiting
First Posted : November 1, 2009
Results First Posted : June 2, 2014
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Melanoma
Interventions Procedure: Surgery
Drug: Administration of Lymphodepletion
Other: Adoptive Cell Transfer
Drug: High Dose IL-2
Enrollment 19
Recruitment Details Participants were recruited at Moffitt Cancer Center from October 20, 2009 until November 15, 2012.
Pre-assignment Details  
Arm/Group Title TIL With High Dose IL-2
Hide Arm/Group Description

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours.

Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.

Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.

Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Surgery: Surgery to remove a tumor for growth of TIL

Administration of Lymphodepletion: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Adoptive Cell Transfer: T-cell infusion

High Dose IL-2: Beginning approximately 12 - 16 hours after cell infusion.

Period Title: Overall Study
Started 19
Completed 13
Not Completed 6
Reason Not Completed
No TIL growth             1
Disease progressed during TIL growth             3
Death prior to treatment             1
Inappropriate antidiuretic hormone             1
Arm/Group Title TIL With High Dose IL-2
Hide Arm/Group Description

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours.

Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.

Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.

Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Surgery: Surgery to remove a tumor for growth of TIL

Administration of Lymphodepletion: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Adoptive Cell Transfer: T-cell infusion

High Dose IL-2: Beginning approximately 12 - 16 hours after cell infusion.

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
All 19 participants accrued are listed for baseline, Primary Outcome Measure and Adverse Events. All 13 participants who completed treatment are listed for analysis of Secondary Outcome Measure.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants
46.5
(25 to 68)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
  78.9%
>=65 years
4
  21.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
7
  36.8%
Male
12
  63.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
1.Primary Outcome
Title Number of Participants With Tumor Infiltrating Lymphocytes (TIL) Growth
Hide Description Feasibility was the primary endpoint of this trial, defined as a patient who can grow and expand T-cells: Number of participants with fragments cultured; Number of participants with fragments that reached a final count of 20e6 cells within 5 weeks of culture; Number of participants with fragments that reached a final count of 20e6 cells within 5 weeks of culture and were cocultured with autologous or human leukocyte antigen (HLA)-matched tumor cells for interferon(IFN)-γ production; Number of participants with fragments that produced IFN-γ in response to autologous or HLA-matched tumor cells.
Time Frame 192 Days Post Surgical Resection
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title TIL With High Dose IL-2
Hide Arm/Group Description:

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours.

Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.

Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.

Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Surgery: Surgery to remove a tumor for growth of TIL

Administration of Lymphodepletion: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Adoptive Cell Transfer: T-cell infusion

High Dose IL-2: Beginning approximately 12 - 16 hours after cell infusion.

Overall Number of Participants Analyzed 19
Measure Type: Number
Unit of Measure: participants
Participants with fragments cultured 19
Participants with fragments grown 14
Participants with fragments tested 14
Participants with IFN-γ positive fragments 13
2.Secondary Outcome
Title Number of Participants With Objective Response (OR)
Hide Description OR is defined as the patient being alive at Day 70 and tumor size evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria to be a complete response or partial response. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Evaluations were made by computed tomography (CT) scan approximately 6 to 8 weeks after the cell infusion, or CT scan approximately 10 weeks after the cell infusion, or by clinical evaluation during the first 70 days.
Time Frame Average of 10 Months Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who completed treatment
Arm/Group Title TIL With High Dose IL-2
Hide Arm/Group Description:

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours.

Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.

Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.

Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Surgery: Surgery to remove a tumor for growth of TIL

Administration of Lymphodepletion: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Adoptive Cell Transfer: T-cell infusion

High Dose IL-2: Beginning approximately 12 - 16 hours after cell infusion.

Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: participants
Partial Response (PR) 3
Complete Response (CR) 2
Complete Response (PR + CR) 5
Time Frame 3 years
Adverse Event Reporting Description All participants
 
Arm/Group Title TIL With High Dose IL-2
Hide Arm/Group Description

Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hour infused intravenously over 24 hours.

Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.

Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.

Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.

Surgery: Surgery to remove a tumor for growth of TIL

Administration of Lymphodepletion: Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo

Adoptive Cell Transfer: T-cell infusion

High Dose IL-2: Beginning approximately 12 - 16 hours after cell infusion.

All-Cause Mortality
TIL With High Dose IL-2
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
TIL With High Dose IL-2
Affected / at Risk (%) # Events
Total   7/19 (36.84%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/19 (5.26%)  1
Cardiac disorders   
Atrial fibrillation  1  1/19 (5.26%)  1
Ear and labyrinth disorders   
Hearing impaired  1  1/19 (5.26%)  1
Eye disorders   
Cataract  1  1/19 (5.26%)  1
Uveitis  1  1/19 (5.26%)  1
Gastrointestinal disorders   
Constipation  1  1/19 (5.26%)  1
Nausea  1  2/19 (10.53%)  2
Vomiting  1  3/19 (15.79%)  3
General disorders   
Fatigue  1  1/19 (5.26%)  1
Fever  1  1/19 (5.26%)  1
Infections and infestations   
Bladder infection  1  1/19 (5.26%)  1
Investigations   
Blood antidiuretic hormone abnormal  1  1/19 (5.26%)  1
Urine output decreased  1  1/19 (5.26%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/19 (5.26%)  1
Hyponatremia  1  1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other - basal cell carcinoma  1  1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Invasive squamous cell  1  1/19 (5.26%)  2
Renal and urinary disorders   
Acute kidney injury  1  1/19 (5.26%)  1
Cystitis noninfective  1  1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/19 (5.26%)  1
Pleural effusion  1  1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders - Other - pulmonary edema  1  1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TIL With High Dose IL-2
Affected / at Risk (%) # Events
Total   14/19 (73.68%)    
Blood and lymphatic system disorders   
Anemia  1  13/19 (68.42%)  71
Febrile neutropenia  1  9/19 (47.37%)  9
Blood and lymphatic system disorders - Other  1  7/19 (36.84%)  24
Cardiac disorders   
Sinus tachycardia  1  10/19 (52.63%)  14
Atrial fibrillation  1  3/19 (15.79%)  3
Cardiac disorders - Other  1  3/19 (15.79%)  4
Chest pain - cardiac  1  1/19 (5.26%)  1
Myocarditis  1  1/19 (5.26%)  1
Sinus bradycardia  1  1/19 (5.26%)  1
Supraventricular tachycardia  1  1/19 (5.26%)  1
Ear and labyrinth disorders   
Ear and labyrinth disorders - Other  1  1/19 (5.26%)  1
Hearing impaired  1  1/19 (5.26%)  1
Tinnitus  1  1/19 (5.26%)  1
Vertigo  1  1/19 (5.26%)  1
Eye disorders   
Blurred vision  1  2/19 (10.53%)  2
Flashing lights  1  2/19 (10.53%)  3
Cataract  1  1/19 (5.26%)  1
Photophobia  1  1/19 (5.26%)  1
Uveitis  1  1/19 (5.26%)  1
Gastrointestinal disorders   
General disorders and administration site - Other  1  3/19 (15.79%)  4
Nausea  1  13/19 (68.42%)  19
Vomiting  1  10/19 (52.63%)  15
Diarrhea  1  9/19 (47.37%)  12
Constipation  1  3/19 (15.79%)  5
Mucositis oral  1  3/19 (15.79%)  4
Abdominal pain  1  1/19 (5.26%)  1
Anal hemorrhage  1  1/19 (5.26%)  1
Dysphagia  1  1/19 (5.26%)  1
Gastroparesis  1  1/19 (5.26%)  1
General disorders   
Fatigue  1  14/19 (73.68%)  32
Chills  1  13/19 (68.42%)  17
Edema - limbs  1  5/19 (26.32%)  9
Pain  1  3/19 (15.79%)  3
Fever  1  2/19 (10.53%)  3
Edema - trunk  1  1/19 (5.26%)  1
Immune system disorders   
Cytokine release syndrome  1  3/19 (15.79%)  3
Immune system disorders - Other  1  3/19 (15.79%)  4
Infections and infestations   
Bladder infection  1  1/19 (5.26%)  1
Skin infection  1  1/19 (5.26%)  3
Investigations   
Platelet count decreased  1  13/19 (68.42%)  84
White blood cell decreased  1  13/19 (68.42%)  52
Alkaline phosphatase increased  1  10/19 (52.63%)  19
Blood bilirubin increased  1  10/19 (52.63%)  23
Alanine aminotransferase increased  1  8/19 (42.11%)  11
Creatinine increased  1  8/19 (42.11%)  13
Lymphocyte count decreased  1  8/19 (42.11%)  27
Aspartate aminotransferase increased  1  7/19 (36.84%)  12
Neutrophil count decreased  1  7/19 (36.84%)  22
Activated partial thromboplastin time prolonged  1  1/19 (5.26%)  1
Blood antidiuretic hormone abnormal  1  1/19 (5.26%)  1
Investigations - Other  1  1/19 (5.26%)  1
Urine output decreased  1  1/19 (5.26%)  1
Metabolism and nutrition disorders   
Hyponatremia  1  13/19 (68.42%)  29
Hypocalcemia  1  12/19 (63.16%)  43
Hypophosphatemia  1  12/19 (63.16%)  23
Anorexia  1  10/19 (52.63%)  13
Hypoalbuminemia  1  10/19 (52.63%)  42
Hyperglycemia  1  9/19 (47.37%)  25
Hypomagnesemia  1  9/19 (47.37%)  17
Hypokalemia  1  4/19 (21.05%)  7
Hypermagnesemia  1  3/19 (15.79%)  3
Hypoglycemia  1  3/19 (15.79%)  5
Hyperkalemia  1  2/19 (10.53%)  2
Hypernatremia  1  2/19 (10.53%)  2
Acidosis  1  1/19 (5.26%)  1
Dehydration  1  1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders   
Back Pain  1  2/19 (10.53%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other  1  2/19 (10.53%)  2
Nervous system disorders   
Headache  1  5/19 (26.32%)  7
Dizziness  1  2/19 (10.53%)  2
Cognitive disturbance  1  1/19 (5.26%)  1
Depressed level of consciousness  1  1/19 (5.26%)  1
Dysgeusia  1  1/19 (5.26%)  1
Encephalopathy  1  1/19 (5.26%)  1
Sinus pain  1  1/19 (5.26%)  1
Syncope  1  1/19 (5.26%)  1
Vasovagal reaction  1  1/19 (5.26%)  1
Psychiatric disorders   
Confusion  1  4/19 (21.05%)  6
Anxiety  1  3/19 (15.79%)  3
Insomnia  1  3/19 (15.79%)  3
Depression  1  2/19 (10.53%)  2
Delirium  1  1/19 (5.26%)  3
Renal and urinary disorders   
Acute kidney injury  1  3/19 (15.79%)  8
Urinary retention  1  3/19 (15.79%)  3
Proteinuria  1  2/19 (10.53%)  2
Bladder spasm  1  1/19 (5.26%)  1
Cystitis noninfective  1  1/19 (5.26%)  1
Hematuria  1  1/19 (5.26%)  3
Renal and urinary disorders - Other  1  1/19 (5.26%)  2
Urinary frequency  1  1/19 (5.26%)  1
Urinary incontinence  1  1/19 (5.26%)  1
Urinary tract pain  1  1/19 (5.26%)  2
Urine discoloration  1  1/19 (5.26%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  9/19 (47.37%)  10
Hypoxia  1  5/19 (26.32%)  5
Pleural effusion  1  4/19 (21.05%)  5
Respiratory, thoracic and mediastinal disorders - Other  1  4/19 (21.05%)  4
Epistaxis  1  3/19 (15.79%)  3
Hiccups  1  3/19 (15.79%)  3
Pulmonary edema  1  3/19 (15.79%)  3
Cough  1  2/19 (10.53%)  2
Adult respiratory distress syndrome  1  1/19 (5.26%)  1
Allergic rhinitis  1  1/19 (5.26%)  1
Bronchospasm  1  1/19 (5.26%)  1
Laryngeal edema  1  1/19 (5.26%)  1
Pneumonitis  1  1/19 (5.26%)  1
Sore throat  1  1/19 (5.26%)  1
Skin and subcutaneous tissue disorders   
Alopecia  1  6/19 (31.58%)  6
Rash maculo-papular  1  5/19 (26.32%)  5
Pruritus  1  3/19 (15.79%)  3
Skin and subcutaneous tissue disorders - Other  1  3/19 (15.79%)  4
Dry skin  1  2/19 (10.53%)  2
Hyperhidrosis  1  1/19 (5.26%)  1
Vascular disorders   
Hypotension  1  9/19 (47.37%)  9
Capillary leak syndrome  1  4/19 (21.05%)  4
Vascular disorders - Other  1  4/19 (21.05%)  5
Flushing  1  2/19 (10.53%)  2
Hot flashes  1  2/19 (10.53%)  2
Hypertension  1  1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE v4.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Amod Sarnaik, M.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-8581
EMail: amod.sarnaik@moffitt.org
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01005745    
Other Study ID Numbers: MCC-15781
First Submitted: October 27, 2009
First Posted: November 1, 2009
Results First Submitted: May 1, 2014
Results First Posted: June 2, 2014
Last Update Posted: February 18, 2020