Metastatic Melanoma
Conditions
Brief summary
The purpose of this protocol is to determine whether autologous TIL infused in conjunction with systemic high-dose IL-2 after non-myeloablative chemotherapy with cyclophosphamide and fludarabine can cause consistent and durable objective responses in patients who have metastatic melanoma at the John Wayne Cancer Institute (JWCI).
Interventions
BIOLOGICALTumor Infiltrating Lymphocytes (TIL)
Patients will receive an IV adoptive transfer of at least 10\^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down.
Sponsors
Saint John's Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- * Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size and be willing to undergo such a resection for experimental purposes. * Patients must be \> 18 years of age. * Patients must have measurable disease measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (in addition to the resected lesion). * Patients of child bearing potential must agree to use an effective form of birth control during study and up to four months after receiving treatment. * Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1. * Absolute neutrophil count greater than 1000/mm3 without support of filgrastim. * Platelet count greater than 100,000/mm3. * Serum Alanine transaminase/Aspartate transaminase (ALT/AST) less than three times the upper limit of normal. * Serum creatinine less than or equal to 1.6 mg/dl. * Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl. * Patients must be able to understand and sign the Informed Consent document.
Exclusion criteria
- Tumor/TIL Harvest
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response | 12 weeks, or until development of new metastases or recurrence | At the end of 12 week follow up, the proportion of patients that showed clinical response (CR) determined by the disappearance of all target lesions, or partial response (PR) will be calculated. The patient is determined to have partial response as if 30% reduction in the sum of the longest diameter (SLD) of target lesions are shown from the baseline sum LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life | 12 weeks, or until development of new metastases or recurrence | Quality of Life will be assessed and scored per European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) EORTC-QLQ-C30 version 3.0 requirements. The EORTC QLQ-C30 contains subscales for global health status, and physical, emotional, role, cognitive and social function with higher scores indicating better functioning (19). The change in QOL measured throughout the study period will be examined through mixed effect model adjusting for the baseline. Akaike information criteria (AIC) will be used to determine appropriate covariance structure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tumor Infiltrating Lymphocytes (TIL) Patients will have a melanoma metastasis resected and cultured in IL-2 in vitro either as part of this treatment protocol or the JWCI procurement protocol. TIL from these cultures will be assessed for tumor-reactivity and those with such activity will be further expanded and adoptively transferred. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day X 2 days IV) and fludarabine (25 mg/m2/day IV X 5 days). Following this regimen, patients will receive an intravenous adoptive transfer of at least 109 tumor-reactive lymphocytes (TIL) followed by high-dose intravenous IL-2 (600-720,000 IU/kg/dose every 8 hours for up to 12 doses).
Tumor Infiltrating Lymphocytes (TIL): Patients will receive an IV adoptive transfer of at least 10\^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Tumor Infiltrating Lymphocytes (TIL) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 21.986 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Clinical Response
At the end of 12 week follow up, the proportion of patients that showed clinical response (CR) determined by the disappearance of all target lesions, or partial response (PR) will be calculated. The patient is determined to have partial response as if 30% reduction in the sum of the longest diameter (SLD) of target lesions are shown from the baseline sum LD.
Time frame: 12 weeks, or until development of new metastases or recurrence
Population: Single patient treated, no formal statistical analysis performed
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL) | Clinical Response | Complete Responder | 0 Participants |
| Tumor Infiltrating Lymphocytes (TIL) | Clinical Response | Partial Responder | 0 Participants |
| Tumor Infiltrating Lymphocytes (TIL) | Clinical Response | Non Responder | 1 Participants |
Secondary
Quality of Life
Quality of Life will be assessed and scored per European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) EORTC-QLQ-C30 version 3.0 requirements. The EORTC QLQ-C30 contains subscales for global health status, and physical, emotional, role, cognitive and social function with higher scores indicating better functioning (19). The change in QOL measured throughout the study period will be examined through mixed effect model adjusting for the baseline. Akaike information criteria (AIC) will be used to determine appropriate covariance structure.
Time frame: 12 weeks, or until development of new metastases or recurrence
Population: Although the single participant completed a total of 3 surveys, these were never scored or analyzed and data are not available to be reported.