Metastatic Melanoma, Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7
Conditions
Brief summary
This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.
Detailed description
PRIMARY OBJECTIVES: I. To assess the feasibility and safety of CXCR2 and NGFR transduced tumor-infiltrating lymphocytes (TIL) for treating metastatic malignant melanoma. SECONDARY OBJECTIVES: I. Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. II. Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL. III. Characterize the clinical response and correlate with migration of CXCR2 transduced TIL to the tumor and levels of CXCL1 and CXCL8 at the tumor site. OUTLINE: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses). After completion of study treatment, patients are followed up at weeks 6 and 12, every 3 months for a year, and then annually for up to 15 years.
Interventions
BIOLOGICALAldesleukin
Given IV
BIOLOGICALCXCR2-transduced Autologous Tumor Infiltrating Lymphocytes
Given IV
DRUGCyclophosphamide
Given IV
DRUGFludarabine Phosphate
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALNGFR-transduced Autologous T Lymphocytes
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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
* TURNSTILE I INCLUSION CRITERIA: * Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease (Turnstile I) * Patients must have a lesion amenable to resection for the generation of TIL (Turnstile I) * Patients must receive a magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) of the brain within 6 months of signing informed consent; if new lesions are present, patient must have definitive treatment; principal investigator (PI) or his designee should make final determination regarding enrollment (Turnstile I) * Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 within 30 days of signing informed consent (Turnstile I) * Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee * Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP); a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (Turnstile I) * CHEMOTHERAPY/CELL INFUSION INCLUSION CRITERIA: * Patients must have adequate TIL available (Turnstile II) * Patients must have at least one biopsiable and measurable metastatic melanoma lesions \>= 1 cm (Turnstile II) * Patients may have brain lesions which measure =\< 1 cm each (Turnstile II) * Patients of both genders must practice birth control for four months after receiving the preparative regimen (lymphodepletion) and continue to practice birth control throughout the study; patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery (Turnstile II) * Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is an acceptable form of birth control (Turnstile II) * Pregnancy testing will be performed within 14 days prior to treatment (Turnstile II) * Clinical performance status of ECOG 0-2 within 14 days of lymphodepletion (Turnstile II) * Absolute neutrophil count greater than or equal to 1000/mm\^3 (Turnstile II) * Platelet count greater than or equal to 100,000/mm\^3 (Turnstile II) * Hemoglobin greater than or equal to 8.0 g/dl (Turnstile II) * Serum alanine transaminase (ALT) less than three times the upper limit of normal (Turnstile II) * Serum creatinine less than or equal to 1.6 mg/dl (Turnstile II) * Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl (Turnstile II) * A stress cardiac test (stress thallium, stress multigated acquisition \[MUGA\] scan, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion (Turnstile II) * Forced expiratory volume in 1 second (FEV1) \> 65% of predicted within 6 months of lymphodepletion (Turnstile II) or * Forced vital capacity (FVC) \> 65% of predicted within 6 months of lymphodepletion (Turnstile II) * MRI/CT/PET of the brain within 30 days of lymphodepletion
Exclusion criteria
* Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; PI or his designee shall make the final determination regarding appropriateness of enrollment (Turnstile I) * Patients who are pregnant or nursing (Turnstile I) * CHEMOTHERAPY/CELL INFUSION
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immune-Related Response | Up to 1 year | Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline. Response will be evaluated by positron emission tomography or computed tomography imaging. |
| Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities | Up to 8 weeks | Possible grade 3 or worse toxicities not normally associated with lymphodepletion and high dose IL-2 will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CXCR2 Transduction | At infusion | Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. his is a statistical version of the intuitive idea that, if the TIL methodology works as designed and the genetically transduced T-cells differentially recognize the cancer cell cytokines, then the ratio of post- and pre-treatment ratios RR = RY/RX should be larger than 1. |
| CXCL1 and CXCL8 Chemokines Produced | At infusion | Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL |
| Characterize the Clinical Response and Correlate With Migration of CXCR2 Transduced TIL to the Tumor and Levels of CXCL1 and CXCL8 at the Tumor Site. | At infusion | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Genetically Modified T-cells, High-dose Aldesleukin Participants receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Participants then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses).
Aldesleukin: Given IV
CXCR2-transduced Autologous Tumor Infiltrating Lymphocytes: Given IV
Cyclophosphamide: Given IV
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
NGFR-transduced Autologous T Lymphocytes: Given IV
Quality-of-Life Assessment: Ancillary studies | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 1 |
| Overall Study | Screen failure | 1 |
Baseline characteristics
| Characteristic | Treatment (Genetically Modified T-cells, High-dose Aldesleukin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| 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 | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 8 / 8 |
Outcome results
Primary
Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities
Possible grade 3 or worse toxicities not normally associated with lymphodepletion and high dose IL-2 will be reported.
Time frame: Up to 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Genetically Modified T-cells, High-dose Aldesleukin | Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities | 8 Participants |
Primary
Number of Participants With Immune-Related Response
Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline. Response will be evaluated by positron emission tomography or computed tomography imaging.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Genetically Modified T-cells, High-dose Aldesleukin | Number of Participants With Immune-Related Response | 8 Participants |
Secondary
Characterize the Clinical Response and Correlate With Migration of CXCR2 Transduced TIL to the Tumor and Levels of CXCL1 and CXCL8 at the Tumor Site.
Time frame: At infusion
Population: Data were not collected
Secondary
CXCL1 and CXCL8 Chemokines Produced
Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL
Time frame: At infusion
Population: Data were not collected
Secondary
CXCR2 Transduction
Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. his is a statistical version of the intuitive idea that, if the TIL methodology works as designed and the genetically transduced T-cells differentially recognize the cancer cell cytokines, then the ratio of post- and pre-treatment ratios RR = RY/RX should be larger than 1.
Time frame: At infusion
Population: Data were not collected