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

1. 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.

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.

What this study is about