A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue
Nationwide Children's Hospital
Summary
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
Description
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 w…
Eligibility
- Age range
- 2–40 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Patients must be between the ages ≥ 2 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. 2. Patients must have measurable disease using RECIST 1.1 criteria 3. Patients must have had at least one and no more than four total lines of cytotoxic systemic treatment for relapse sarcoma. Local control with surgical resection or radiation therapy of the primary tumor and any metastatic sites as clinically indicated as standard of care per the treating physician must be cons…
Interventions
- BiologicalGEM/DOX + TGFBi expanded NK cells
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)
Locations (22)
- University of AlabamaSouth Birmingham, Alabama
- Phoenix Children's HospitalPhoenix, Arizona
- Arkansas Children's HospitalLittle Rock, Arkansas
- Children's Hospital of Los AngelesLos Angeles, California
- Stanford UniversityPalo Alto, California
- University of FloridaGainesville, Florida