The purpose of this study is to determine if the addition of infusions of a type of immune cell called a "natural killer", or NK cell to the sarcoma chemotherapy regimen GEM/DOX (gemcitabine and docetaxel) can improve outcomes in people with childhood sarcomas that have relapsed or not responded to prior therapies. The goals of this study are: * To determine the safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory pediatric sarcomas To determine the 6-month progression free survival achieved with this treatment in patients within cohorts of relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma. * To identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells Participants will receive study drugs that include chemotherapy and NK cells in cycles; each cycle is 21 days long and you can receive up to 8 cycles. * Gemcitabine (GEM): via IV on Days 1 and 8 * Docetaxel (DOX): via IV on Day 8 * Prophylactic dexamethasone: Day 7-9 to prevent fluid retention and hypersensitivity reaction * Peg-filgrastim (PEG-GCSF) or biosimilar: Day 9 to help your white blood cell recover and allow more chemotherapy to be given * TGFβi NK cells: via IV on Day 12
This is a multi-center study with rolling safety and toxicity analysis, to determine the safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory pediatric sarcomas, identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells, and assess in vivo persistence of expanded, universal donor, TGFβi NK cells after adoptive transfer and correlate with clinical outcomes. The planned therapy will involve 8 cycles of 21 days each consisting of gemcitabine, docetaxel, supportive dexamethasone and peg-filgrastim, and universal donor, TGFβi ex vivo expanded NK cells (Cycles 1-6).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
8 cycles consisting of gemcitabine, docetaxel, supportive dexamethasone and pegfilagrastim, and universal donor, TGFBi ex vivo expanded NK cells * Each cycle will be repeated every 21 days based upon disease response and toxicity criteria * Tumor response assessed after Cycles 2, 4, 6, and 8 1. Gemcitabine 675mg/m2/dose IV on Days 1 and 8 2. Docetaxel 75mg/m2/dose IV on Day 8 3. Dexamethasone 3mg/m2/dose (max 8 mg/dose) PO BID on Days 7, 8, and 9 4. Pegfilgrastim (Peg-GCSF) 0.1mg/kg/dose (max 6 mg/dose) SQ on Day 9 5. NK cells 1 x 10e8 cells/kg/dose IV on Day 12 (+ 1-2 days)
University of Alabama
South Birmingham, Alabama, United States
RECRUITINGPhoenix Children's Hospital
Phoenix, Arizona, United States
RECRUITINGArkansas Children's Hospital
Little Rock, Arkansas, United States
RECRUITINGChildren's Hospital of Los Angeles
Los Angeles, California, United States
RECRUITINGStanford University
Palo Alto, California, United States
RECRUITINGUniversity of Florida
Gainesville, Florida, United States
RECRUITINGNemours Jacksonville
Jacksonville, Florida, United States
RECRUITINGUniversity of Miami
Miami, Florida, United States
RECRUITINGJohns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
RECRUITINGWashington University/St Louis Childrens
St Louis, Missouri, United States
RECRUITING...and 12 more locations
Part 1
Evaluation of DLT in patients enrolled during Part 1 enrollment * ≥2 of 6 patients with DLT will be cause for termination of the study
Time frame: 3-5 years
Part 2
Determination of 6-month progression free survival (PFS) in study patients measured from initiation of treatment (Day 1 of the first cycle of therapy) Patients will be considered evaluable for tumor response if they: * Have received at least one dose of NK cell infusion * Have completed all therapy and are 1 year from initiation of treatment * Are lost to follow up * Elect to discontinue therapy * Terminate treatment for reasons of toxicity or progression prior to completion of therapy.
Time frame: 3-5 years
Treatment response of target lesions determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Assessments will be performed after every other cycle of treatment to determine antitumor effect of therapy.
Time frame: Every two cycles (21 days per cycle) for 3-5 years
Frequency and characterization of DLT in study patients
cycle = 21 days
Time frame: 3-5 years
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