Trial Outcomes & Findings for Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma (NCT NCT02408016)

NCT ID: NCT02408016

Last Updated: 2021-09-13

Results Overview

Based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 6 months after the first T cell infusion

Results posted on

2021-09-13

Participant Flow

11 participants were enrolled, but only 10 participants were assigned to an arm/group.

Participant milestones

Participant milestones
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Study STARTED	6	4
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection
Overall Study Death	6	1	0
Overall Study Physician Decision	0	2	0

Baseline Characteristics

Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) n=6 Participants Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) n=4 Participants Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	0 Participants n=7 Participants	—	4 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	—	6 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	—	6 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	—	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	—	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	4 Participants n=7 Participants	—	10 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	4 participants n=7 Participants	—	10 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 6 months after the first T cell infusion

Population: No patients were treated in Arm II.

Based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Outcome measures

Outcome measures
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) n=6 Participants Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) n=4 Participants Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection
Number of Participants With Adverse Events	6 Participants	3 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

Population: No patients were treated in Arm II.

There were products generated for 11 participants and 10 participants were treated on the study. 8 participants received an infusion with Tn and Tcm cells. 1 participant received infusions with only Tn cells. 1 participant received their last infusion with only Tcm cells. The one participant that was not treated did successfully have Tn and Tcm cells generated but they were not treated due to their condition worsening.

Outcome measures

Outcome measures
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) n=6 Participants Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) n=4 Participants Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection
Count of Patients for Which T Cells Are Successfully Generated and Infused and Whether Only TN or TCM Could be Generated	4 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 100 days after the last T cell infusion

Population: No patients were treated in Arm II

In vivo persistence of cells generated from the TN subset with cells generated from the TCM subset will be directly compared within each patient by high throughput T-cell receptor (TCR) beta sequencing. The one-sample T test will be used to assess the difference in mean persistence between groups, in which the outcome for each patient is the time to disappearance of infused cytotoxic T lymphocytes.

Outcome measures

Outcome measures
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) n=6 Participants Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) n=4 Participants Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection
Persistence of Transduced T Cells	NA Participants This outcome could not be assessed. Although we detected persistence if T cells by tetramer staining in all patients, the transduced cells came from the endogenous repertoire from each patient. As the pre-T cell infusion leaves were elevated, we could not detect changes in TN vs TCM using high-throughput TCR sequencing.	NA Participants This outcome could not be assessed. Although we detected persistence if T cells by tetramer staining in all patients, the transduced cells came from the endogenous repertoire from each patient. As the pre-T cell infusion leaves were elevated, we could not detect changes in TN vs TCM using high-throughput TCR sequencing.	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 15 years

Frequency of transferred T cells at biopsied tumor sites between the Tn and Tcm groups will be assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 15 years

Tetramer+ cells from peripheral blood, if detectable and available in sufficient number, evaluated for production of intracellular cytokines including interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-2. Intranuclear Ki-67 expression assessed on recovered tetramer+ T cells. Based on available numbers, ex vivo proliferative capacity after infusion assessed by labeling cells with carboxyfluorescein succinimidyl ester dye and measuring dilution in response to peptide stimulation. Phenotype of tetramer+ antigen-specific cells assessed using established immunophenotyping

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months after last infusion

The potential efficacy of the infused cells will be assessed and the substrate cell (TN or TCM) that is most effective based on the TTP of patients who have persisting TN cells to that of patients who have persisting TCM cells 3 months after the last infusion will be determined.

Outcome measures

Outcome data not reported

Adverse Events

Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 6 deaths

Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Arm II (T Lymphocytes, IL-2, Surgery)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm I, Stage I (T Lymphocytes, Cyclophosphamide, IL-2) n=6 participants at risk Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on days 0 and 14, cyclophosphamide IV on days 11 and 12, and aldesleukin SC BID for 14 days. Patients who have received radiation to the chest/lung tissue may receive gene-transduced T lymphocytes 90 days after completion of radiation. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm I, Stage II (T Lymphocytes, Cyclophosphamide, IL-2) n=4 participants at risk Patients receive cyclophosphamide IV on days -3 and -2, autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV on day 0, and aldesleukin SC BID for 14 days. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Cyclophosphamide: Given IV Laboratory Biomarker Analysis: Correlative studies	Arm II (T Lymphocytes, IL-2, Surgery) Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days. Patients then undergo surgery within 3-4 weeks after the T-cell infusion. Aldesleukin: Given SC Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes: Given IV Laboratory Biomarker Analysis: Correlative studies Therapeutic Conventional Surgery: Undergo surgical resection
General disorders Fever	33.3% 2/6 • Number of events 2 • 12 months No patients were treated in Arm II.	0.00% 0/4 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Investigations Lymphocyte count decreased	100.0% 6/6 • Number of events 9 • 12 months No patients were treated in Arm II.	75.0% 3/4 • Number of events 3 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Metabolism and nutrition disorders Hyponatremia	16.7% 1/6 • Number of events 1 • 12 months No patients were treated in Arm II.	0.00% 0/4 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1 • 12 months No patients were treated in Arm II.	0.00% 0/4 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Vascular disorders Hypertension	16.7% 1/6 • Number of events 1 • 12 months No patients were treated in Arm II.	0.00% 0/4 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Blood and lymphatic system disorders Anemia	0.00% 0/6 • 12 months No patients were treated in Arm II.	25.0% 1/4 • Number of events 1 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
General disorders Fatigue	0.00% 0/6 • 12 months No patients were treated in Arm II.	25.0% 1/4 • Number of events 2 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Investigations White blood cell count decreased	0.00% 0/6 • 12 months No patients were treated in Arm II.	25.0% 1/4 • Number of events 1 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.
Investigations Neutrophil count decreased	0.00% 0/6 • 12 months No patients were treated in Arm II.	25.0% 1/4 • Number of events 1 • 12 months No patients were treated in Arm II.	— 0/0 • 12 months No patients were treated in Arm II.

Additional Information

Dr. Aude Chapuis

FHCRC

Phone: 2066674369

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place