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Pediatric Sarcoma, RefractoryPhase 1/2TINKSNCT05634369

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

A Phase 1/2 study testing GEM/DOX + TGFBi expanded NK cells in people with Pediatric Sarcoma, Refractory and Pediatric Sarcoma, Relapsed, run by Nationwide Children's Hospital at 22 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 40 years
What is being tested?
GEM/DOX + TGFBi expanded NK cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
22 sitesUnited States
Study dates
14 Nov 2022to 1 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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.
  • 4) 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
  • Serum creatinine < 1.5 x upper limit of normal based on age/gender (Table 3) OR creatinine clearance ≥70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Shortening fraction ≥ 27% by ECHO OR ejection fraction of ≥ 50% by ECHO or gated radionuclide study
  • Echocardiogram done within 12 months of study entry will be acceptable. If patient has required anthracycline chemotherapy since last ECHO and enrollment on this study, echocardiogram should be repeated.
  • No evidence for dyspnea at rest, no chronic oxygen requirement, and room air pulse oximetry >94% if there is a clinical indication for pulse oximetry 6) Neuropathy: Patients must have ≤ Grade 2 neuropathy at enrollment 7) Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsant, with the exception of diazepam given its potential deleterious effects on NK cell activity.
  • 8) Contraception: The effects of expanded NK cells on the developing human fetus are unknown. For this reason and because the chemotherapeutic preparative agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of preparatory regimen administration.
  • 9) All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document.

Who cannot join

  • 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:
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  • 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.
  • Concomitant Medications:
  • Due to their effect on NK cell function, systemic corticosteroids outside of the supportive dexamethasone given from day 7 through 9 should be used ONLY for life-threatening conditions (i.e., life-threatening allergic reactions and anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The use of dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy can be used as a premedication for transfusion in patients known to have a history of transfusion reactions or for treatment of an unexpected transfusion reaction (hydrocortisone 2 mg/kg or less or an equivalent dose of an alternative corticosteroids). The use of steroids during protocol therapy other than the study- required prophylactic dexamethasone doses requires clear justification and documentation of use for a life-threatening condition.
  • The following are also prohibited while on study treatment
  • Strong CYP3A4 inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information.
  • Diazepam
  • Chemotherapeutic agents other than the study drugs
  • Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection
  • psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnancy or Breast-Feeding: Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies with Gemcitabine and Docetaxel
  • HIV Infection: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study medications. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jessica Crimella, BSN, RN, CCRP contact

813-745-6250

jessica.crimella@moffitt.org

22 sites in 1 country

United States22 sites, 22 recruiting

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

    Ajay Gupta, MD, 716-845-2333, Ajay.Gupta@RoswellPark.org

    Ajay Gupta, MD

    Recruiting

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

    Patrick Thompson, MD, 919-966-1178, patom@email.unc.edu

    Patrick Thompson, MD

    Recruiting

  • Levine Cancer Institute

    Charlotte, North Carolina, 28203

    Erin M Trovillion, MD, 704-381-9900, Erin.Trovillion@atriumhealth.org

    Erin M Trovillion, MD

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Matteo Trucco, MD, 216 444-9085, TRUCCOM@ccf.org

    Matteo Trucco, MD

    Recruiting

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

    Clelie Peck, 6147225634, clelie.peck@nationwidechildrens.org

    Bhuvana Setty, MD

    Recruiting

  • UT Southwestern

    Dallas, Texas, 75390

    Avanthi Shah, MD, 214-456-2382, Avanthi.Shah@UTSouthwestern.edu

    Avanthi Shah, MD

    Recruiting

  • Duke Children's Hospital/Duke Health

    Durham, North Carolina, 27710

    Jessica Sun, MD, 919-668-1102, jessica.sun@duke.edu

    Jessica Sun, MD

    Recruiting

  • University of Florida

    Gainesville, Florida, 32610

    John Ligon, MD, 352-273-9120, john.ligon@ufl.edu

    John Ligon, MD

    Recruiting

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Irtiza Sheikh, MD, 832-728-9791, isheikh1@mdanderson.org

    Jonathan Gill, MD, 713-745-3145, jbgill@mdanderson.org

    Recruiting

  • Nemours Jacksonville

    Jacksonville, Florida, 32207

    Anderson Collier, III, MD, 904-697-3793, Anderson.Collier@nemours.org

    Anderson Collier, III, MD

    Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

    David Douglas, MD, 501-364-1494, dpdouglass@uams.edu

    David Douglas, MD

    Recruiting

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

    Fariba Navid, MD, 323-361-2121, fnavid@chla.usc.edu

    Fariba Navid, MD

    Recruiting

  • University of Miami

    Miami, Florida, 33136

    Aditi Dhir, MD, 305-243-4830, aditi.dhir@med.miami.edu

    Aditi Dhir, MD

    Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

    Scott Borinstein, MD, 615-936-1762, scott.c.borinstein@vumc.org

    Scott Borinstein, MD

    Recruiting

  • Stanford University

    Palo Alto, California, 94304

    Raya Hamad Saab, MD, 650-723-5535, rsaab@stanford.edu

    Raya Hamad Saab, MD

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Jacquelyn W Crane, MD, 215-290-2299, cranej2@chop.edu

    Jacquelyn W Crane, MD

    Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Mona Nourani, MD, 602-933-0920, mnourani@phoenixchildrens.com

    Mona Nourani, MD

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Matthew Dietz, DO, 801-662-4700, matthew.dietz@hsc.utah.edu

    Matthew Dietz, DO

    Recruiting

  • University of Alabama

    South Birmingham, Alabama, 35233

    Elizabeth Alva, MD, 205-683-9285, ealva@peds.uab.edu

    Elizabeth Alva, MD

    Recruiting

  • Washington University/St Louis Childrens

    St Louis, Missouri, 63110

    Amy Armstrong, MD, 314-454-6018, armstrongae@wustl.edu

    Amy Armstrong, MD

    Recruiting

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

    Natalie Booth, DO, 727-767-3513, nbooth3@jh.edu

    Natalie Booth, DO

    Recruiting

  • Montefiore Medical Center

    The Bronx, New York, 10467

    Alice Lee, MD, 718-741-2342, alee5@montefiore.org

    Alice Lee, MD

    Recruiting

Other trials in United States

About this study

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:

Read more
  • 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
Read the 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).

Being tested
GEM/DOX + TGFBi expanded NK cells
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GEM/DOX + TGFBi expanded NK cellsBiological

    Also called Docetaxel, Dexamethasone, Pegfilgrastim, Gemcitabine

    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)
Study groups in NCT05634369
Study groupRoleWhat they receive
TreatmentExperimentalPart 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.
Receives: Biological: GEM/DOX + TGFBi expanded NK cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3-5 years

  2. 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.

    Measured: 3-5 years

Secondary outcomes (2)

  1. 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.

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

  2. Frequency and characterization of DLT in study patients

    cycle = 21 days

    Measured: 3-5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2022
  2. Study start14 Nov 2022
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm, unblinded, phase I/II study
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05634369
Sponsor's protocol ID
MCC21704
Acronym
TINKS
Status last verified
Jan 2026
First submitted
15 Nov 2022
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GEM/DOX + TGFBi expanded NK cells in people with Pediatric Sarcoma, Refractory and Pediatric Sarcoma, Relapsed, run by Nationwide Children's Hospital at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jessica Crimella, BSN, RN, CCRP (813-745-6250, jessica.crimella@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 (time frame: 3-5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05634369.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.

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