NCT05634369

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 2 Years – 40 Years
• Healthy volunteers: Not accepted

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

Detailed 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 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).

Conditions

• Pediatric Sarcoma, Refractory
• Pediatric Sarcoma, Relapsed

Interventions

Type	Name	Description
BIOLOGICAL	GEM/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)

Timeline

• Start date: 2022-11-14
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2022-12-02
• Last updated: 2026-01-28

Locations

22 sites across 1 country: United States

Regulatory

• FDA-regulated drug study