RECRUITING

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

Conditions

Pediatric Sarcoma, Refractory Pediatric Sarcoma, Relapsed

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2022-11-14

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05634369

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 40 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients must be between the ages \> 12 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. 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 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. * Absolute Neutrophil Count ≥1000/mcL * Platelet count ≥100,000/mcL independent of transfusion * 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.	1. Patients who are receiving any other investigational agents. 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 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 7. Patients with CNS metastatic disease will not be eligible for this study. 8. 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 9. Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * psychiatric illness/social situations that would limit compliance with study requirements 10. 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 11. 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 12. 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.

Inclusion Criteria

Exclusion Criteria

1. Patients must be between the ages \> 12 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma.
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 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.
* Absolute Neutrophil Count ≥1000/mcL
* Platelet count ≥100,000/mcL independent of transfusion
* 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.

1. Patients who are receiving any other investigational agents.
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 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
7. Patients with CNS metastatic disease will not be eligible for this study.
8. 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
9. Uncontrolled intercurrent illness including, but not limited to:
* ongoing or active infection
* psychiatric illness/social situations that would limit compliance with study requirements
10. 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
11. 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
12. 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.

Contacts and Locations

Study Contact

Jessica Crimella, BSN, RN, CCRP

CONTACT

813-745-6250

jessica.crimella@moffitt.org

Principal Investigator

Bhuvana Setty, MD

PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Study Locations (Sites)

University of Alabama

South Birmingham, Alabama, 35233

United States

Children's Hospital of Los Angeles

Los Angeles, California, 90027

United States

University of Florida

Gainesville, Florida, 32610

United States

Nemours Jacksonville

Jacksonville, Florida, 32207

United States

University of Miami

Miami, Florida, 33136

United States

Johns Hopkins All Children's Hospital

Saint Petersburg, Florida, 33701

United States

Washington University/St Louis Childrens

Saint Louis, Missouri, 63110

United States

Montefiore Medical Center

Bronx, New York, 10467

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

United States

Levine Cancer Institute

Charlotte, North Carolina, 28203

United States

Duke Children's Hospital/Duke Health

Durham, North Carolina, 27710

United States

Nationwide Children's Hospital

Columbus, Ohio, 43205

United States

UT Southwestern

Dallas, Texas, 75390

United States

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Primary Children's Hospital

Salt Lake City, Utah, 84113

United States

Collaborators and Investigators

Sponsor: Nationwide Children's Hospital

Bhuvana Setty, MD, PRINCIPAL_INVESTIGATOR, Nationwide Children's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-14

Study Completion Date2027-12

Study Record Updates

Study Start Date2022-11-14

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Pediatric Sarcoma, Refractory
Pediatric Sarcoma, Relapsed