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

NCT05634369 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC21704
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 22

Brief 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

Conditions

Pediatric Sarcoma, Refractory; Pediatric Sarcoma, Relapsed

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  3-5 years

Secondary Outcomes (2)

• Treatment response of target lesions determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Every two cycles (21 days per cycle) for 3-5 years

• Frequency and characterization of DLT in study patients

  3-5 years

Other Outcomes (1)

• Exploratory Endpoint

  Days 1, 8, and 12 of each cycle (21 days per cycle), starting with cycle 2

Study Arms (1)

Treatment

EXPERIMENTAL

Part 1: Enrollment of 5 patients in each cohort (osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and non-rhabdomyosarcoma). Part 2: Enrollment of 2 cohorts in 2 stages for a total of 40 patients.

Biological: GEM/DOX + TGFBi expanded NK cells

Interventions

GEM/DOX + TGFBi expanded NK cells BIOLOGICAL

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)

Also known as: Docetaxel, Dexamethasone, Pegfilgrastim, Gemcitabine

Treatment

Eligibility Criteria

• Age: 2 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Prior Therapy: Therapy may not have been received more recently than the timeframes defined below:
• Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 14 days of protocol therapy
• Radiation: At least 2 weeks must have elapsed from the start of protocol therapy since local palliative XRT (small port); 4 weeks must have elapsed for all other radiation therapy
• Hematopoietic Cell Transplant (HCT): Patients must have at least 6 weeks elapsed after autologous and allogeneic hematopoietic cell transplant
• Biologic (anti-neoplastic agent): At least 7 days or 5 half-lives of the drug, whichever is longer, must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent.
• Monoclonal antibodies: At least 3 weeks must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody.
• Prior use of Gemcitabine and/or Docetaxel: Patients who have received these agents for prior treatment may be included if previous treatments were given ≥ 6 months prior to enrollment on this study, and there were no allergic reactions, pulmonary edema or fibrosis, Grade 3 or higher neuropathy or other non-hematologic Grade 4 adverse events related to gemcitabine and/or docetaxel therapies.
• \) Performance status: Karnofsky ≥ 60 for patients ≥16 years of age. Lansky score of ≥ 60 for patients \< 16 years of age (see Appendix A) 5) Organ Function Requirements: Patients must have normal organ and marrow function within 7 days of starting protocol therapy as defined below:
• Absolute Neutrophil Count ≥1000/mcL
• Platelet count ≥100,000/mcL transfusion independent defined as no platelet transfusions within the last 72 hours
• Total bilirubin \< 1.5x upper limit of normal for age
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal

You may not qualify if:

• 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.
• Patients with bone marrow only disease are not eligible for this study.
• Patients with any of the following "Intermediate" (rarely metastasizing) or "malignant" Grade 2 or Grade 3 tumors of any size, as defined in the WHO Classification of Soft Tissue Tumors are not eligible for this study:
• So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues
• Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma
• Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumour, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), initial sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor
• Chondro-osseous tumors - extraskeletal osteosarcoma
• Pericytic (perivascular) tumors - malignant glomus tumor
• Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor
• Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
• Patients who, in the judgment of the treating physician, has tumors near critical structures for which transient swelling would cause substantial symptoms, such as tumor within the bowel mucosa
• Patients with CNS metastatic disease will not be eligible for this study.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• National Pediatric Cancer Foundation: collaborator

Study Sites (22)

University of Alabama

South Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Nemours Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Washington University/St Louis Childrens

St Louis, Missouri, 63110, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Duke Children's Hospital/Duke Health

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75390, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

Docetaxel; Dexamethasone; pegfilgrastim; Gemcitabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Bhuvana Setty, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Crimella, BSN, RN, CCRP

CONTACT

813-745-6250; jessica.crimella@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, unblinded, phase I/II study

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: December 2, 2022
• Study Start: November 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (22)