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
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.
Patients must have measurable disease using RECIST 1.1 criteria
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 considered prior to enrollment.
Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 14 days of protocol therapy
Patients who are receiving any other investigational agents.
Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
Patients with a history of allergic reactions attributed to docetaxel, gemcitabine, or peg-filgrastim or biosimilar
Patients who have received any prior cellular therapies, such as CAR-T cells or other expanded or manufactured cellular products.
Single group
GEM/DOX + TGFBi expanded NK cells
Biological/Vaccine8 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)
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
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.
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.
Frequency and characterization of DLT in study patients
cycle = 21 days
Exploratory Endpoint
Assessment of TGFβi NK cell persistence, phenotype, and retained cytolytic activity in patient peripheral blood via samples drawn on days 1, 8, and 12 of each cycle beginning with cycle 2 analyzed by flow cytometry.
Click on the lead sponsor to view all of their trials.
Nationwide Children's Hospital
Lead sponsor
National Pediatric Cancer Foundation
Collaborator
