Trial Outcomes & Findings for Immunotherapy Using 41BB Selected Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma (NCT NCT02111863)

Last Updated: 2017-09-19

Results Overview

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

2 years and 59 days

Results posted on

2017-09-19

Participant Flow

Participant milestones

Participant milestones
Measure	Lymphocyte Depleting Prep Regimen Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Immunotherapy Using 41BB Selected Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lymphocyte Depleting Prep Regimen n=6 Participants Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	49.8 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years and 59 days

Outcome measures

Outcome measures
Measure	Lymphocyte Depleting Prep Regimen n=6 Participants Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Count of Participants With Serious and Non-Serious Adverse Events	6 Participants

PRIMARY outcome

Timeframe: approximately 2 years

Objective response is defined as complete response + partial response and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. 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 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.

Outcome measures

Outcome measures
Measure	Lymphocyte Depleting Prep Regimen n=6 Participants Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Objective Response Rate of Patients With Metastatic Melanoma Progressive Disease	83.33 percentage of participants
Objective Response Rate of Patients With Metastatic Melanoma Partial Response	16.67 percentage of participants
Objective Response Rate of Patients With Metastatic Melanoma Complete Response	0 percentage of participants
Objective Response Rate of Patients With Metastatic Melanoma Stable Disease	0 percentage of participants

SECONDARY outcome

Timeframe: up to 3 years

OS is defined as the time between the first day of treatment to the day of death or date last known alive.

Outcome measures

Outcome measures
Measure	Lymphocyte Depleting Prep Regimen n=6 Participants Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Overall Survival (OS) of Patients Receiving a Lymphocyte Depleting Preparative Regimen	12 months Interval 2.0 to 35.0

Adverse Events

Lymphocyte Depleting Prep Regimen

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lymphocyte Depleting Prep Regimen n=6 participants at risk Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin. Aldesleukin: Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses). Fludarabine: Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4) Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml 5% dextrose in water (D5W) over 1 hr. 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL): On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).
Blood and lymphatic system disorders Hemoglobin	66.7% 4/6 • Number of events 4 • 2 years and 59 days
Blood and lymphatic system disorders Leukocytes (total WBC)	50.0% 3/6 • Number of events 3 • 2 years and 59 days
Blood and lymphatic system disorders Lymphopenia	100.0% 6/6 • Number of events 6 • 2 years and 59 days
Blood and lymphatic system disorders Neutrophils/granulocytes	100.0% 6/6 • Number of events 6 • 2 years and 59 days
Blood and lymphatic system disorders Platelets	100.0% 6/6 • Number of events 6 • 2 years and 59 days
General disorders Fatigue (asthenia, lethargy, malaise)	66.7% 4/6 • Number of events 4 • 2 years and 59 days
Gastrointestinal disorders Distension/bloating, abdominal	16.7% 1/6 • Number of events 1 • 2 years and 59 days
Infections and infestations Infection	33.3% 2/6 • Number of events 2 • 2 years and 59 days
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	16.7% 1/6 • Number of events 1 • 2 years and 59 days
Nervous system disorders Psychosis (hallucinations/delusions)	16.7% 1/6 • Number of events 1 • 2 years and 59 days

Additional Information

Dr. Steven A. Rosenberg

National Cancer Institute

Phone: 301-496-4164

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place