Tumor Infiltrating Lymphocytes for the Treatment of Children with High Risk Solid Tumors

Inclusion Criteria

• PART ONE: Patients must be ≥ 1 year to ≤ 21 years of age at time of enrollment to part one
• PART ONE: Diagnosis * Initial therapy patients: Patients with a histologic diagnosis of high-risk pediatric extra-cranial malignant solid tumors (pMST), defined as a pediatric malignant solid tumor outside of the central nervous system (CNS), newly-diagnosed or being treated with initial therapy, with expected 5-year event free survival (EFS) < 60% are eligible. Eligible diagnoses include: ** High-risk neuroblastoma ** Metastatic Ewing sarcoma ** Metastatic osteosarcoma ** Hepatoblastoma metastatic or not amenable to total resection ** Desmoplastic small round cell tumor ** Metastatic rhabdomyosarcoma ** Metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) ** Metastatic diffuse anaplastic Wilms tumor ** Malignant rhabdoid tumor of kidney or liver ** Mediastinal mixed germ cell tumors ** Other tumors may be deemed eligible after assessment and documentation of prognosis of expected 5-year EFS <60% from an enrolling institution’s multidisciplinary tumor board. ***Note: melanoma will not be considered a pMST for this study and will not be eligible ***Note: There will be occasions prior to establishment of a histologic diagnosis where an investigator will highly suspect one of the diagnoses above in a patient due to undergo a surgical procedure (initial biopsy, up-front resection, etc.). If this is the case, the investigator may choose to enroll the patient prior to a tissue diagnosis. Their suspicion of a qualifying diagnosis should be documented. If the diagnosis is confirmed, the patient may continue on study. If the diagnosis is not confirmed, the patient will be considered a screening failure and removed from study. * Relapsed/refractory/recurrent patients: patients with a histologic diagnosis of high risk pMST outside the CNS (may include diagnoses outside those identified above for initial therapy patients) that has relapsed after achieving remission or progressed after completion of all planned initial therapy are eligible
• PART ONE: Patients must have a planned open surgical biopsy or resection (core needle/final needle biopsies are not allowed) for standard of care purposes, at some point in their initial or relapsed therapy for pMST. * Note: The planned surgery for tissue procurement may occur at any time during initial therapy including up-front surgeries or after neoadjuvant therapies, including chemotherapy, immunotherapy, and radiation
• PART ONE: All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document
• PART TWO: ≥ 1-year-old at enrollment.* There is no upper bound age limit, as long as the patient met age criteria at the time of enrollment on part one. * Note: To protect the safety of patients in this first pediatric study of TIL therapy, the first two patients to receive TIL therapy must be ≥ 12 years of age at the time of enrollment
• PART TWO: Weight ≥ 5 kg at time of enrollment for part two
• PART TWO: Confirmation of satisfactory TIL cellular product availability
• PART TWO: Karnofsky/Lansky (as age appropriate) score ≥ 60%.
• PART TWO: Disease Status: * Non-neuroblastoma solid tumors: Patients must have a histologic diagnosis of high-risk pMST as defined in part one inclusion and have recurrent/refractory local disease considered unresectable and/or metastatic disease for which standard curative measures do not exist or are no longer effective. Patients must have disease that is measurable or evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Neuroblastoma: Patient must have high-risk neuroblastoma according to Children’s Oncology Group (COG) risk stratification at the time of enrollment that is A) recurrent or B) refractory after a minimum of four cycles of induction chemotherapy
• PART TWO: Absolute neutrophil count ≥ 1000/mm^3, greater than 7 days from short-acting myeloid growth factors and at least 14 days from long-acting myeloid growth factors (within 7 days prior to starting the protocol therapy)
• PART TWO: Platelet count ≥ 100,000/mm^3 without transfusion within 7 days and without platelet growth factors for at least 14 days (within 7 days prior to starting the protocol therapy)
• PART TWO: Hemoglobin ≥ 8.0 g/dL without transfusion within 14 days (within 7 days prior to starting the protocol therapy)
• PART TWO: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 5 x the institutional upper limit of normal (within 7 days prior to starting the protocol therapy)
• PART TWO: Total bilirubin < 2.0 mg/dL (within 7 days prior to starting the protocol therapy)
• PART TWO: Serum creatinine within normal limits based on age/gender OR creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m^2 (within 7 days prior to starting the protocol therapy) * 1 to < 2 years: Maximum serum creatinine 0.6 mg/dL (male), 0.6 mg/dL (female) * 2 to < 6 years: Maximum serum creatinine 0.8 mg/dL (male), 0.8 mg/dL (female) * 6 to < 10 years: Maximum serum creatinine 1 mg/dL (male), 1 mg/dL (female) * 10 to < 13 years: Maximum serum creatinine 1.2 mg/dL (male), 1.2 mg/dL (female) * 13 to < 16 years: Maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female) * >= 16 years: Maximum serum creatinine 1.7 mg/dL (male),1.4 mg/dL (female)
• PART TWO: Shortening fraction ≥ 27% by echocardiogram OR ejection fraction > 50% by echocardiogram or radionuclide angiogram (within 7 days prior to starting the protocol therapy)
• PART TWO: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 92% on room air (within 7 days prior to starting the protocol therapy)
• PART TWO: Prior Therapy: Therapy may not have been received more recently than the timeframes defined below: * Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy. * Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea) * Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. * Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. * Cellular therapy: ≥ 42 days must have elapsed from last dose of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.) * Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥ 21 days must have elapsed from the last dose of interleukins, interferon or cytokines (other than hematopoietic growth factors). * Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1. * Radiation: At least 28 days after local palliative radiation (XRT) (small port); 6 weeks must have elapsed since treatment with therapeutic doses of 131I-MIBG; At least 42 days must have elapsed if other substantial bone marrow (BM) radiation. * Stem Cell Infusion without total body irradiation (TBI): No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant and 42 days for autologous stem cell infusion after 131IMIBG therapy. * Investigational agents not otherwise specified: ≥ 30 days must have elapsed since the last dose of any agents not specified above. For agents with an uncertain washout period or for any questions or uncertainty the study principal investigator (PI) should be notified.
• PART TWO: Contraception: patients of childbearing potential must agree to use an effective contraceptive method from the time of informed consent, for the duration of study treatment, and for 1 month following completion of protocol treatment. The definition of an effective contraceptive method will be at the discretion of the institutional investigator
• PART TWO: All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document (separate from part one consent)

Exclusion Criteria

• PART ONE: Patients with CNS diagnoses or metastatic disease to the CNS, currently active or in the past, are not eligible for this study
• PART ONE: Patients with bone marrow only disease are not eligible for this study
• PART ONE: Patients with melanoma are not eligible for this study
• PART TWO: Patients with active systemic infections requiring intravenous antibiotics
• PART TWO: Patients testing positive for HIV titer, hepatitis B surface antigen, human T-cell leukemia-lymphoma virus (HTLV) I or II antibody, or both rapid plasma regain (RPR) and fluorescent treponemal antibody (FTA) are excluded. Patients with hepatitis C antibody must have a negative (undetectable) viral load by polymerase chain reaction (PCR)
• PART TWO: Patients with a history of hypersensitivity reaction to any components of the study intervention, including any component of the TIL product formulation
• PART TWO: Patients who have received any live vaccines within 30 days prior to enrollment
• PART TWO: Patients with a history of clinically significant chronic obstructive pulmonary disease, asthma, interstitial lung disease, or other chronic lung disease
• PART TWO: Patients with a history of or active uveitis
• PART TWO: Patients who are pregnant or breastfeeding
• PART TWO: Patients needing chronic immunosuppressive systemic steroids are excluded. Any supraphysiologic doses of steroids must be discontinued by the time of enrollment
• PART TWO: Patients with autoimmune diseases that require immunosuppressive medications
• PART TWO: Patients with central nervous system metastases, currently active or in the past
• PART TWO: Patients with history of prior solid organ transplant
• PART TWO: Patients receiving concomitant anti-cancer therapies or investigational therapies
• PART TWO: Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible