Trial Outcomes & Findings for Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes (NCT NCT00509288)
NCT ID: NCT00509288
Last Updated: 2012-12-28
Results Overview
Tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is 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 is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
7/5/07-4/23/09
Results posted on
2012-12-28
Participant Flow
Participant milestones
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
Patients treated with peripheral blood lymphocytes (PBL). A minimum of approximately 5 X 10\^8 cells will be given up to 3x10\^11 anti-MART-1 F5 TCR engineered TIL or PBL. Day -7 to -5: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml D5W with mesna 15 mg/kg/day X 2 days over 1 hr. Day -5 to 1: Fludarabine 25 mg/m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days. Day 0: Cells will be infused intravenously (i.v.). Patients will receive up to 3x10e\^11 (with a minimum of 5x10e\^8 cells) anti-MART-1 F5 TCR engineered TIL or PBL Aldesleukin (based on total body weight) 720,000 IU/kg intravenous (IV) over 15 minute every eight hours beginning within 24 hours of cell infusion.
|
Anti-MART-1 F5 TCR TIL + HD IL-2
Patients treated with tumor infiltrating lymphocytes (TIL). A minimum of approximately 5 X 10\^8 cells will be given up to 3x10\^11 anti-MART-1 F5 TCR engineered TIL or PBL. Day -7 to -5: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml D5W with mesna 15 mg/kg/day X 2 days over 1 hr. Day -5 to 1: Fludarabine 25 mg/m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days Day 0: Cells will be infused intravenously (i.v.). Patients will receive up to 3x10e\^11 (with a minimum of 5x10e\^8 cells) anti-MART-1 F5 TCR engineered TIL or PBL Aldesleukin (based on total body weight) 720,000 IU/kg intravenous (IV) over 15 minute every eight hours beginning within 24 hours of cell infusion.
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
3
|
|
Overall Study
COMPLETED
|
21
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes
Baseline characteristics by cohort
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
n=21 Participants
Patients treated with peripheral blood lymphocytes (PBL).
|
Anti-MART-1 F5 TCR TIL + HD IL-2
n=3 Participants
Patients treated with tumor infiltrating lymphocytes (TIL).
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
21 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
45.9 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
48.0 years
STANDARD_DEVIATION 21.7 • n=7 Participants
|
46.2 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=5 Participants
|
3 participants
n=7 Participants
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7/5/07-4/23/09Tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is 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 is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Outcome measures
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
n=21 Participants
Patients treated with peripheral blood lymphocytes (PBL).
|
Anti-MART-1 F5 TCR TIL + HD IL-2
n=3 Participants
Patients treated with tumor infiltrating lymphocytes (TIL).
|
|---|---|---|
|
Clinical Tumor Regression.
Complete Response
|
0 Participants
|
0 Participants
|
|
Clinical Tumor Regression.
Partial Response
|
6 Participants
|
0 Participants
|
|
Clinical Tumor Regression.
Progressive Disease
|
15 Participants
|
2 Participants
|
|
Clinical Tumor Regression.
Stable Disease
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 57 monthsHere is the number of participants with adverse events. For a detailed listing of adverse events, see the adverse event module.
Outcome measures
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
n=21 Participants
Patients treated with peripheral blood lymphocytes (PBL).
|
Anti-MART-1 F5 TCR TIL + HD IL-2
n=3 Participants
Patients treated with tumor infiltrating lymphocytes (TIL).
|
|---|---|---|
|
Toxicity
|
21 Participants
|
3 Participants
|
Adverse Events
Anti-MART-1 F5 TCR PBL + HD IL-2
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Anti-MART-1 F5 TCR TIL + HD IL-2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
n=21 participants at risk
Patients treated with peripheral blood lymphocytes (PBL).
|
Anti-MART-1 F5 TCR TIL + HD IL-2
n=3 participants at risk
Patients treated with tumor infiltrating lymphocytes (TIL).
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Infections and infestations
Infection (documented clinically or microbiologically)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Infections and infestations
Infection with unknown ANC
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Creatinine
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
9.5%
2/21 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
Other adverse events
| Measure |
Anti-MART-1 F5 TCR PBL + HD IL-2
n=21 participants at risk
Patients treated with peripheral blood lymphocytes (PBL).
|
Anti-MART-1 F5 TCR TIL + HD IL-2
n=3 participants at risk
Patients treated with tumor infiltrating lymphocytes (TIL).
|
|---|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram
|
47.6%
10/21 • Number of events 11
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Otitis, middle ear (non-infectious)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Ear and labyrinth disorders
Tinnitus
|
14.3%
3/21 • Number of events 5
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemoglobin
|
52.4%
11/21 • Number of events 12
|
100.0%
3/3 • Number of events 4
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
95.2%
20/21 • Number of events 22
|
100.0%
3/3 • Number of events 3
|
|
Blood and lymphatic system disorders
Lymphopenia
|
95.2%
20/21 • Number of events 25
|
100.0%
3/3 • Number of events 3
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
95.2%
20/21 • Number of events 23
|
100.0%
3/3 • Number of events 3
|
|
Blood and lymphatic system disorders
Platelets
|
95.2%
20/21 • Number of events 22
|
100.0%
3/3 • Number of events 3
|
|
Cardiac disorders
Prolonged QTc interval
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia
|
52.4%
11/21 • Number of events 12
|
0.00%
0/3
|
|
Cardiac disorders
Vasovagal episode
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Cardiac disorders
Hypertension
|
14.3%
3/21 • Number of events 3
|
0.00%
0/3
|
|
Cardiac disorders
Hypotension
|
47.6%
10/21 • Number of events 14
|
66.7%
2/3 • Number of events 2
|
|
Cardiac disorders
left ventricular systolic dysfunction
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
PTT (Partial Thromboplastin Time)
|
23.8%
5/21 • Number of events 5
|
66.7%
2/3 • Number of events 2
|
|
General disorders
Constitutional Symptoms-Other (Specify, insomnia)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
38.1%
8/21 • Number of events 9
|
66.7%
2/3 • Number of events 2
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
33.3%
7/21 • Number of events 11
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Insomnia
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Rigors, chills
|
23.8%
5/21 • Number of events 6
|
0.00%
0/3
|
|
General disorders
Sweating (diaphoresis)
|
9.5%
2/21 • Number of events 2
|
0.00%
0/3
|
|
General disorders
Weight loss
|
33.3%
7/21 • Number of events 8
|
33.3%
1/3 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Flushing
|
4.8%
1/21 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Hyperpigmentation
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Hypopigmentation
|
23.8%
5/21 • Number of events 5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
71.4%
15/21 • Number of events 23
|
66.7%
2/3 • Number of events 2
|
|
Gastrointestinal disorders
Anorexia
|
19.0%
4/21 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
|
Gastrointestinal disorders
Ascites (non-malignant)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhea
|
23.8%
5/21 • Number of events 5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
19.0%
4/21 • Number of events 6
|
33.3%
1/3 • Number of events 1
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
9.5%
2/21 • Number of events 2
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
23.8%
5/21 • Number of events 5
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hematoma
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemorrhage, pulmonary/upper respiratory
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)
|
19.0%
4/21 • Number of events 5
|
0.00%
0/3
|
|
Infections and infestations
Infection (documented clinically or microbiologically)
|
14.3%
3/21 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Infections and infestations
Infection with unknown ANC
|
9.5%
2/21 • Number of events 4
|
0.00%
0/3
|
|
Infections and infestations
Febrile neutropenia
|
81.0%
17/21 • Number of events 19
|
66.7%
2/3 • Number of events 2
|
|
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
4.8%
1/21 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
57.1%
12/21 • Number of events 14
|
100.0%
3/3 • Number of events 3
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
28.6%
6/21 • Number of events 7
|
33.3%
1/3 • Number of events 1
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
19.0%
4/21 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hyperglycemia)
|
23.8%
5/21 • Number of events 5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
28.6%
6/21 • Number of events 7
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
23.8%
5/21 • Number of events 6
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
23.8%
5/21 • Number of events 6
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
9.5%
2/21 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
|
Nervous system disorders
CNS cerebrovascular ischemia
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Confusion
|
57.1%
12/21 • Number of events 14
|
33.3%
1/3 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
23.8%
5/21 • Number of events 7
|
0.00%
0/3
|
|
Nervous system disorders
Encephalopathy
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Mental status
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Mood alteration
|
9.5%
2/21 • Number of events 3
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy: cranial
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Psychosis (hallucinations/delusions)
|
19.0%
4/21 • Number of events 4
|
0.00%
0/3
|
|
Nervous system disorders
Speech impairment (e.g., dysphasia or aphasia)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Tremor
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Eye disorders
Dry eye syndrome
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Eye disorders
Eyelid dysfunction
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Eye disorders
Uveitis
|
61.9%
13/21 • Number of events 15
|
0.00%
0/3
|
|
Eye disorders
Vision-blurred vision
|
9.5%
2/21 • Number of events 2
|
0.00%
0/3
|
|
General disorders
Pain
|
81.0%
17/21 • Number of events 60
|
33.3%
1/3 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
9.5%
2/21 • Number of events 2
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.8%
1/21 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
42.9%
9/21 • Number of events 9
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
28.6%
6/21 • Number of events 7
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)
|
14.3%
3/21 • Number of events 3
|
0.00%
0/3
|
|
Renal and urinary disorders
Urinary retention (including neurogenic bladder
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Vascular disorders
Acute vascular leak syndrome
|
76.2%
16/21 • Number of events 19
|
100.0%
3/3 • Number of events 4
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Syncope (fainting)
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
0.00%
0/21
|
33.3%
1/3 • Number of events 1
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
9.5%
2/21 • Number of events 2
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Creatinine
|
4.8%
1/21 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
4.8%
1/21 • Number of events 1
|
0.00%
0/3
|
Additional Information
Dr. Steven Rosenberg
National Cancer Institute, National Institutes of Health
Phone: 301-496-4164
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place