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
NCT ID: NCT05634369
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
50 participants
INTERVENTIONAL
2022-11-14
2027-12-01
Brief Summary
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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
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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
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment
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.
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)
Interventions
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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)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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 considered prior to enrollment.
4. 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.
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.
Exclusion Criteria
2. Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
3. Patients with a history of allergic reactions attributed to docetaxel, gemcitabine, or peg-filgrastim or biosimilar
4. Patients who have received any prior cellular therapies, such as CAR-T cells or other expanded or manufactured cellular products.
5. Patients with bone marrow only disease are not eligible for this study.
6. 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
7. 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
8. Patients with CNS metastatic disease will not be eligible for this study.
9. 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
10. Uncontrolled intercurrent illness including, but not limited to:
* ongoing or active infection
* psychiatric illness/social situations that would limit compliance with study requirements
11. 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
12. 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
13. 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.
2 Years
40 Years
ALL
No
Sponsors
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National Pediatric Cancer Foundation
OTHER
Nationwide Children's Hospital
OTHER
Responsible Party
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Principal Investigators
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Bhuvana Setty, MD
Role: PRINCIPAL_INVESTIGATOR
Nationwide Children's Hospital
Locations
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University of Alabama
South Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Children's Hospital of Los Angeles
Los Angeles, California, United States
University of Florida
Gainesville, Florida, United States
Nemours Jacksonville
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Washington University/St Louis Childrens
St Louis, Missouri, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Duke Children's Hospital/Duke Health
Durham, North Carolina, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
UT Southwestern
Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Countries
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Central Contacts
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Facility Contacts
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Elizabeth Alva, MD
Role: primary
Mona Nourani, MD
Role: primary
David Douglas, MD
Role: primary
Fariba Navid, MD
Role: primary
John Ligon, MD
Role: primary
Anderson Collier, III, MD
Role: primary
Aditi Dhir, MD
Role: primary
Natalie Booth, DO
Role: primary
Amy Armstrong, MD
Role: primary
Ajay Gupta, MD
Role: primary
Alice Lee, MD
Role: primary
Erin M Trovillion, MD
Role: primary
Jessica Sun, MD
Role: primary
Clelie Peck
Role: primary
Jacquelyn W Crane, MD
Role: primary
Scott Borinstein, MD
Role: primary
Avanthi Shah, MD
Role: primary
Irtiza Sheikh, MD
Role: primary
Jonathan Gill, MD
Role: backup
Matthew Dietz, DO
Role: primary
Other Identifiers
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MCC21704
Identifier Type: -
Identifier Source: org_study_id