Trial Outcomes & Findings for Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma (NCT NCT01807182)

Last Updated: 2022-11-10

Results Overview

Assessed using Response Evaluation Criteria in Solid Tumors 1.1 definitions for complete response, partial response, stable disease, and progressive disease. Clinical response will be determined at 6 weeks, 12 weeks and 24 weeks based on RECIST version 1.137 definitions for Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). Response reported is best response per participant. A complete response will be defined as total regression of all tumors, a PR as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and PD as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter (RECIST v1.1 criteria).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 24 weeks post infusion

Results posted on

2022-11-10

Participant Flow

A patient counts as enrolled on this study when they sign treatment consent on the study. 11 patients signed treatment consent, however 1 patient did not move on to treatment due to increased edema and bleeding at brain metastasis. 10 patients were treated on study.

Participant milestones

Participant milestones
Measure	Treatment (Tumor Infiltrating Lymphocytes (TIL), Combination Chemotherapy, Aldesleukin) Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Overall Study STARTED	10
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Tumor Infiltrating Lymphocytes (TIL), Combination Chemotherapy, Aldesleukin) Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Overall Study Death	1
Overall Study New therapy	1
Overall Study Moved to hospice care	1

Baseline Characteristics

Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=10 Participants Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 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	9 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	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks post infusion

Outcome measures

Outcome measures
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=10 Participants Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Number of Participants in Each Clinical Response Category Complete Response	2 Participants
Number of Participants in Each Clinical Response Category Partial Response	2 Participants
Number of Participants in Each Clinical Response Category Progressive Disease	2 Participants
Number of Participants in Each Clinical Response Category Stable Disease	4 Participants

SECONDARY outcome

Timeframe: Up to 24 months

Population: Due to the technical challenges and costs of examining persistence of unmodified TIL cells that do not have a unique tag, the persistence has not been performed in the other patients.

Whole exome and RNA sequencing of tumor cells and normal tissue was performed to identify non synonymous missense mutations, which was then used to generate peptide pools to identify neoantigen-reactive T cells. T-Cell Receptor (TCR) sequencing of T cell clonotypes in blood at time of treatment, 10 months and 24 months was performed and used to assess the persistence of a tumor antigen specific clonotype infused in the TIL product.

Outcome measures

Outcome measures
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=1 Participants Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Number of Participants Who Experienced in Vivo Persistence of Adoptively Transferred T Cells Following TIL Infusion At time of treatment	1 Participants
Number of Participants Who Experienced in Vivo Persistence of Adoptively Transferred T Cells Following TIL Infusion 10 months post infusion	1 Participants
Number of Participants Who Experienced in Vivo Persistence of Adoptively Transferred T Cells Following TIL Infusion 24 months post infusion	1 Participants

SECONDARY outcome

Timeframe: Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion.

Outcome measures

Outcome measures
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=10 Participants Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Count of Participants Who Experienced Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	10 Participants

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Samples from 6 patients were evaluated in depth. Biomarker studies were not performed in all patients due to funding constraints.

Several biomarkers, CXCL13+ CD4 cells, CXCL13+ CD8+ cells, and regulatory cells were evaluated to assess correlation with clinical responses to TIL therapy.

Outcome measures

Outcome measures
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=6 Participants Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
A Count of Participants With Biomarker Expression Above Threshold CXCL13+ as % of CD4 T Cell (40% Threshold)	2 Participants
A Count of Participants With Biomarker Expression Above Threshold Treg as % of CD4 T Cell (40% Threshold)	3 Participants
A Count of Participants With Biomarker Expression Above Threshold CXCL13+ as % of CD8 T Cell (40% Threshold)	6 Participants

Adverse Events

Treatment (TIL, Combination Chemotherapy, Aldesleukin)

Serious events: 4 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=10 participants at risk Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Cardiac disorders Atrial Fibrulation	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Blood and lymphatic system disorders Febrile Neutropenia	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
General disorders Fever	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
General disorders Pain	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Gastrointestinal disorders Vomiting	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.

Other adverse events

Other adverse events
Measure	Treatment (TIL, Combination Chemotherapy, Aldesleukin) n=10 participants at risk Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses. Aldesleukin: Given IV Cyclophosphamide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Tumor Infiltrating Lymphocytes: Undergo TIL infusion
Blood and lymphatic system disorders Anemia	70.0% 7/10 • Number of events 7 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Blood and lymphatic system disorders Febrile neutropenia	70.0% 7/10 • Number of events 7 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Cardiac disorders Sinus tachycardia	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
General disorders Fatigue	20.0% 2/10 • Number of events 2 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
General disorders Fever	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Infections and infestations Catheter related infection	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Infections and infestations Infections and infestations - Other, specify	20.0% 2/10 • Number of events 2 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations Alkaline phosphatase increased	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations Blood bilirubin increased	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations Lymphocyte count decreased	90.0% 9/10 • Number of events 9 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations Neutrophil count decreased	100.0% 10/10 • Number of events 10 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations Platelet count decreased	100.0% 10/10 • Number of events 10 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Investigations White blood cell decreased	90.0% 9/10 • Number of events 9 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Metabolism and nutrition disorders Hyperglycemia	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Metabolism and nutrition disorders Hypernatremia	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Metabolism and nutrition disorders Hypoalbuminemia	20.0% 2/10 • Number of events 2 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Metabolism and nutrition disorders Hyponatremia	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Metabolism and nutrition disorders Hypophosphatemia	70.0% 7/10 • Number of events 7 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Nervous system disorders Dizziness	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Nervous system disorders Somnolence	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Hypoxia	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Stridor	10.0% 1/10 • Number of events 1 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Vascular disorders Hypertension	80.0% 8/10 • Number of events 8 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.
Vascular disorders Hypotension	30.0% 3/10 • Number of events 3 • Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion. All adverse events will be recorded and graded according to the NCI CTCAE version 4.0.

Additional Information

Dr. Sylvia Lee

Fred Hutchinson Cancer Center

Phone: 206-606-2274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place