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Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Anti-gp100:154-162 TCR Gene Engineered Lymphocytes

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ClinicalTrials.gov Identifier: NCT00509496
Recruitment Status : Terminated (Low accrual)
First Posted : July 31, 2007
Results First Posted : December 4, 2012
Last Update Posted : January 15, 2013
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Skin Cancer
Melanoma
Interventions Drug: fludarabine phosphate
Drug: cyclophosphamide
Biological: aldesleukin
Biological: autologous anti-gp 100:154-162 T-cell receptor gene-engineered tumor infiltrating lymphocytes
Biological: autologous anti-gp 100:154-162 T-cell receptor gene-engineered peripheral blood lymphocytes
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Hide Arm/Group Description
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
Period Title: Overall Study
Started 19 2
Completed 19 2
Not Completed 0 0
Arm/Group Title Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2 Total
Hide Arm/Group Description
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
Total of all reporting groups
Overall Number of Baseline Participants 19 2 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 2 participants 21 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
 100.0%
2
 100.0%
21
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 2 participants 21 participants
46.1  (10.5) 28.0  (2.8) 44.4  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 2 participants 21 participants
Female
7
  36.8%
0
   0.0%
7
  33.3%
Male
12
  63.2%
2
 100.0%
14
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 2 participants 21 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
19
 100.0%
2
 100.0%
21
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 2 participants 21 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
19
 100.0%
2
 100.0%
21
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 2 participants 21 participants
19 2 21
1.Primary Outcome
Title Clinical Tumor Regression.
Hide Description Clinical tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD)is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Hide Arm/Group Description:
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
Overall Number of Participants Analyzed 19 2
Measure Type: Number
Unit of Measure: Participants
Complete Response 1 0
Partial Response 2 1
Progressive Disease 16 1
Stable Disease 0 0
2.Secondary Outcome
Title Toxicity
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Hide Arm/Group Description:
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
Overall Number of Participants Analyzed 19 2
Measure Type: Number
Unit of Measure: Participants
19 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Hide Arm/Group Description
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
  1. fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
  2. cyclophosphamide-60 mg/kg/day x 2 days intravenous
  3. Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
  4. aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
All-Cause Mortality
Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/19 (26.32%)      0/2 (0.00%)    
Cardiac disorders     
Hypotension  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Infections and infestations     
Colitis, infectious (e.g., Clostridium difficile)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Infection (documented clinically or microbiologically)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Metabolism and nutrition disorders     
Creatinine  1  3/19 (15.79%)  4 0/2 (0.00%)  0
Nervous system disorders     
Somnolence/depressed level of consciousness  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Renal and urinary disorders     
Renal failure  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnea (shortness of breath)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Pneumonitis/pulmonary infiltrates  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Vascular disorders     
Acute vascular leak syndrome  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Thrombosis/thrombus/embolism  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCv3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Anti-gp100:154-162 TCR PBL + HD IL-2 Anti-gp100:154-162 TCR TIL + HD IL-2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/19 (100.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders     
Hemoglobin  1  15/19 (78.95%)  22 1/2 (50.00%)  1
Leukocytes (total WBC)  1  19/19 (100.00%)  21 2/2 (100.00%)  2
Lymphopenia  1  19/19 (100.00%)  22 2/2 (100.00%)  3
Neutrophils/granulocytes (ANC/AGC)  1  19/19 (100.00%)  22 2/2 (100.00%)  3
Platelets  1  18/19 (94.74%)  18 2/2 (100.00%)  2
PTT (Partial Thromboplastin Time)  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Hemorrhage, GU  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Hemorrhage/Bleeding - Other (hemorrhage)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Cardiac disorders     
Supraventricular and nodal arrhythmia  1  3/19 (15.79%)  3 0/2 (0.00%)  0
Vasovagal episode  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Hypotension  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Ear and labyrinth disorders     
Hearing: patients with/without baseline audiogram  1  8/19 (42.11%)  8 2/2 (100.00%)  2
Tinnitus  1  3/19 (15.79%)  3 2/2 (100.00%)  2
Eye disorders     
Dry eye syndrome  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Nystagmus  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Uveitis  1  6/19 (31.58%)  7 1/2 (50.00%)  1
Vision-blurred vision  1  3/19 (15.79%)  3 1/2 (50.00%)  1
Gastrointestinal disorders     
Anorexia  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Constipation  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Dehydration  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Diarrhea  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Nausea  1  4/19 (21.05%)  4 0/2 (0.00%)  0
Vomiting  1  2/19 (10.53%)  2 0/2 (0.00%)  0
General disorders     
Constitutional Symptoms-Other (Specify, inability to tolerate IL-2)  1  4/19 (21.05%)  4 0/2 (0.00%)  0
Fatigue (asthenia, lethargy, malaise)  1  6/19 (31.58%)  6 0/2 (0.00%)  0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  3/19 (15.79%)  3 1/2 (50.00%)  1
Insomnia  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Weight loss  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Pain  1  3/19 (15.79%)  6 0/2 (0.00%)  0
Infections and infestations     
Infection (documented clinically or microbiologically)  1  3/19 (15.79%)  4 1/2 (50.00%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils  1  3/19 (15.79%)  3 0/2 (0.00%)  0
Infection with unknown ANC  1  2/19 (10.53%)  3 0/2 (0.00%)  0
Febrile neutropenia  1 [1]  10/19 (52.63%)  10 0/2 (0.00%)  0
Metabolism and nutrition disorders     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  1/19 (5.26%)  1 1/2 (50.00%)  1
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  4/19 (21.05%)  4 0/2 (0.00%)  0
Albumin, serum-low (hypoalbuminemia)  1  13/19 (68.42%)  14 1/2 (50.00%)  1
Alkaline phosphatase  1  3/19 (15.79%)  3 0/2 (0.00%)  0
Amylase  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Bilirubin (hyperbilirubinemia)  1  6/19 (31.58%)  6 0/2 (0.00%)  0
Calcium, serum-low (hypocalcemia)  1  8/19 (42.11%)  10 0/2 (0.00%)  0
Creatinine  1  3/19 (15.79%)  3 0/2 (0.00%)  0
Lipase  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Magnesium, serum-high (hypermagnesemia)  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Phosphate, serum-low (hypophosphatemia)  1  7/19 (36.84%)  9 0/2 (0.00%)  0
Potassium, serum-high (hyperkalemia)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Potassium, serum-low (hypokalemia)  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Sodium, serum-low (hyponatremia)  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Uric acid, serum-high (hyperuricemia)  1  3/19 (15.79%)  4 0/2 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle weakness, generalized or specific area (not due to neuropathy)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Nervous system disorders     
Arachnoiditis/meningismus/radiculitis  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Confusion  1  6/19 (31.58%)  6 0/2 (0.00%)  0
Dizziness  1  8/19 (42.11%)  8 0/2 (0.00%)  0
Mood alteration  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Psychosis (hallucinations/delusions)  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Renal and urinary disorders     
Renal failure  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnea (shortness of breath)  1  4/19 (21.05%)  4 2/2 (100.00%)  2
Hypoxia  1  5/19 (26.32%)  5 0/2 (0.00%)  0
Pleural effusion (non-malignant)  1  2/19 (10.53%)  2 0/2 (0.00%)  0
Skin and subcutaneous tissue disorders     
Flushing  1  2/19 (10.53%)  2 2/2 (100.00%)  2
Hyperpigmentation  1  1/19 (5.26%)  1 0/2 (0.00%)  0
Hypopigmentation  1  1/19 (5.26%)  1 1/2 (50.00%)  1
Rash/desquamation  1  16/19 (84.21%)  17 1/2 (50.00%)  1
Vascular disorders     
Acute vascular leak syndrome  1  8/19 (42.11%)  8 1/2 (50.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCv3.0
[1]
(fever of unknown origin without clinically or microbiologically documented infection)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Steven Rosenberg
Organization: National Cancer Institute, National Institutes of Health
Phone: 301-496-4164
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00509496     History of Changes
Other Study ID Numbers: 070174
07-C-0174
First Submitted: July 30, 2007
First Posted: July 31, 2007
Results First Submitted: October 31, 2012
Results First Posted: December 4, 2012
Last Update Posted: January 15, 2013