Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Use of IL-15 After Chemotherapy and Lymphocyte Transfer in 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: NCT01369888
Recruitment Status : Terminated (Closed this protocol due to autoimmune toxicity.)
First Posted : June 9, 2011
Results First Posted : January 27, 2015
Last Update Posted : January 27, 2015
Sponsor:
Information provided by (Responsible Party):
Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Metastatic Melanoma
Skin Cancer
Interventions Drug: Cyclophosphamide
Drug: Fludarabine
Biological: Tumor Infiltrating Lymphocytes
Drug: IL-15
Enrollment 3
Recruitment Details  
Pre-assignment Details Protocol was closed due to autoimmune toxicity unlikely related to cells and probably related to the IL-15 injection seen in one pt and also due to the opening of additional surgery branch protocols suggesting pt accrual would not increase in this protocol. The maximum tolerated dose (MTD) was not determined and it did not enter the phase 2 stage.
Arm/Group Title IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg) IL-15 Following Young TIL (1 mcg) IL-15 Following Young TIL (2 mcg)
Hide Arm/Group Description

0.25 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

0.50 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

1 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

2 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

Period Title: Overall Study
Started 1 2 0 0
Completed 1 2 0 0
Not Completed 0 0 0 0
Arm/Group Title IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg) IL-15 Following Young TIL (10.50 mcg) IL-15 Following Young TIL (2 mcg) Total
Hide Arm/Group Description

0.25 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

0.50 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

1 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

2 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

Total of all reporting groups
Overall Number of Baseline Participants 1 2 0 0 3
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
<=18 years 0 0 0
Between 18 and 65 years 1 2 3
>=65 years 0 0 0
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
61.0 38.  (5.7) 45.7  (13.9)
Gender  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
Female 0 0 0
Male 1 2 3
Ethnicity (NIH/OMB)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
Hispanic or Latino 0 0 0
Not Hispanic or Latino 1 2 3
Unknown or Not Reported 0 0 0
Race (NIH/OMB)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
American Indian or Alaska Native 0 0 0
Asian 0 0 0
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 0 0 0
White 1 2 3
More than one race 0 0 0
Unknown or Not Reported 0 0 0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 1 participants 2 participants 0 participants 0 participants 3 participants
1 2 3
1.Primary Outcome
Title Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
Hide Description Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Hide Arm/Group Description:

0.25 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

0.50 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

Overall Number of Participants Analyzed 1 2
Measure Type: Number
Unit of Measure: mcg/kg/day
NA [1]  NA [1] 
[1]
The MTD was not determined due to the autoimmune toxicity and it did not enter the phase 2 stage.
2.Primary Outcome
Title Number of Participants With Adverse Events
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 8 months, 9 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Hide Arm/Group Description:

0.25 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

0.50 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

Overall Number of Participants Analyzed 1 2
Measure Type: Number
Unit of Measure: participants
1 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Hide Arm/Group Description

0.25 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

0.50 mcg/kg/day x 10

Cyclophosphamide: 60 mg/m^2, intravenous (IV) (in the vein) x 2 days

Fludarabine: 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0

IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

All-Cause Mortality
IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      0/2 (0.00%)    
Immune system disorders     
Autoimmune reaction  1  1/1 (100.00%)  1 0/2 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
IL-15 Following Young TIL (0.25 mcg) IL-15 Following Young TIL (0.50 mcg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders     
Leukocytes (total WBC)  1  1/1 (100.00%)  1 2/2 (100.00%)  2
Lymphopenia  1  1/1 (100.00%)  1 2/2 (100.00%)  2
Neutrophils/granulocytes (ANC/AGC)  1  1/1 (100.00%)  1 2/2 (100.00%)  2
Platelets  1  1/1 (100.00%)  1 2/2 (100.00%)  2
Edema: limb  1  1/1 (100.00%)  1 0/2 (0.00%) 
Ear and labyrinth disorders     
Otitis, middle ear (non-infectious)  1  0/1 (0.00%)  1/2 (50.00%)  1
Endocrine disorders     
Hot flashes/flushes  1  0/1 (0.00%)  1/2 (50.00%)  1
Gastrointestinal disorders     
Mucositis/stomatitis  1  1/1 (100.00%)  1 0/2 (0.00%) 
Anorexia  1  0/1 (0.00%)  1/2 (50.00%)  1
Constipation  1  0/1 (0.00%)  1/2 (50.00%)  1
Nausea  1  0/1 (0.00%)  1/2 (50.00%)  1
General disorders     
Pain  1  1/1 (100.00%)  1 0/2 (0.00%) 
Fatigue (asthenia, lethargy, malaise)  1  0/1 (0.00%)  1/2 (50.00%)  1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  0/1 (0.00%)  1/2 (50.00%)  1
Rigors/chills  1  0/1 (0.00%)  1/2 (50.00%)  1
Sweating (diaphoresis)  1  0/1 (0.00%)  1/2 (50.00%)  1
Weight loss  1  0/1 (0.00%)  1/2 (50.00%)  1
Pain  1  0/1 (0.00%)  2/2 (100.00%)  2
Infections and infestations     
Infection  1  1/1 (100.00%)  1 0/2 (0.00%) 
Febrile neutropenia  1 [1]  0/1 (0.00%)  2/2 (100.00%)  2
Metabolism and nutrition disorders     
Albumin, serum-low (hypoalbuminemia)  1  0/1 (0.00%)  1/2 (50.00%)  1
Calcium, serum-low (hypocalcemia)  1  0/1 (0.00%)  1/2 (50.00%)  1
Magnesium, serum-low (hypomagnesemia)  1  0/1 (0.00%)  1/2 (50.00%)  1
Phosphate, serum-low (hypophosphatemia)  1  0/1 (0.00%)  1/2 (50.00%)  1
Nervous system disorders     
Cognitive disturbances  1  1/1 (100.00%)  1 0/2 (0.00%) 
Psychosis (hallucinations/delusions)  1 [2]  1/1 (100.00%)  1 0/2 (0.00%) 
Syncope (fainting)  1  0/1 (0.00%)  1/2 (50.00%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/1 (100.00%)  1 0/2 (0.00%) 
Dyspnea (shortness of breath)  1  0/1 (0.00%)  1/2 (50.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
(fever of unknown origin without clinically or microbiologically documented infection) (ANC <1.0 x 10e9/L, fever >38.5 degrees C)
[2]
Uninvited visual images when eyes closed.
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
Phone: 301-496-4164
Responsible Party: Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01369888     History of Changes
Other Study ID Numbers: 110170
11-C-0170
First Submitted: June 8, 2011
First Posted: June 9, 2011
Results First Submitted: January 15, 2015
Results First Posted: January 27, 2015
Last Update Posted: January 27, 2015