Phase I/Ib Study of Adoptive NK Expressing an Affinity-enhanced T-cell Receptor (TCR) Reactive Against the NY-ESO-1-specific Cord Blood-derived NK Cells (NY-ESO-1 TCR/IL-15 NK) in Conjunction With Lymphodepleting Chemotherapy for the Management of Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

The goal of this clinical research study is to find a recommended dose of donated NK cells that can be given along with chemotherapy to patients with advanced cancers. The safety and effects of this therapy will also be studied.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 16
Maximum Age: 80
Healthy Volunteers: f
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• Patients with all cancer histology, with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the preenrollment tumor sample, for the dose escalation cohort. NY-ESO expression must be confirmed at MDACC prior to study entry.

• Patients with histologically confirmed synovial sarcoma (cohort 1) or myxoid/round cell liposarcoma (cohort 2), with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the pre-enrollment tumor sample, for the expansion cohorts. Archival samples will be permitted for screening. NY-ESO expression must be confirmed at MDACC prior to study entry.

• Patients must meet disease-specific eligibility criteria (see below).

• Patients must have relapsed or become refractory to standard of care treatment and must have received at least one prior line of systemic therapy including either doxorubicin and/or ifosfamide (synovial sarcoma and MRCLS) or trabectedin (MRCLS).

• Patients must have measurable disease per the RECIST v1.1 at enrollment.

• Patients must be at least 2 weeks from last cytotoxic chemotherapy at the time of first administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least 3 days prior to administration of lymphodepleting chemotherapy.

• Patients must be at least 3 months from any cell therapy for malignancy.

• Eastern Cooperative Oncology Group performance status 0-1 (Appendix A).

• Adequate organ function at screening, as defined by the following:

∙ Renal: Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥45 ml/min/1.73 m2

‣ Hepatic: alanine transaminase (ALT)/aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL or ≤ 3.0 mg/dL for patients with Gilbert's Syndrome. No history of liver cirrhosis and no ascites.

‣ Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)

‣ Pulmonary: No clinically significant pleural effusion (per principal investigator \[PI\] judgement), and baseline oxygen saturation ≥ 92% on room air,

‣ Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL

‣ Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.

⁃ Able to provide written informed consent.

⁃ Aged 16-80 years.

⁃ Weight ≥40 kg.

⁃ All male and female patients who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Female patients who become pregnant or suspect pregnancy must immediately notify their doctor. Females patients who become pregnant will be taken off study. Men who are able to have children must use effective birth control while on the study therapy.

⁃ Acceptable forms of birth control for male patients include: condom with spermicide or abstinence. If the male patient fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.

⁃ Negative serum or urine beta human chorionic gonadotropin pregnancy test for females of childbearing potential (defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females) at screening.

⁃ Signed consent to long-term follow-up on protocol PA17-0483.

⁃ Disease-specific inclusion criteria

⁃ Advanced solid tumors a. Patients with locally advanced and/or metastatic solid tumors may be enrolled in the dose escalation phase. Patients must have received at least one prior line of standard therapy.

• 18 Synovial Sarcoma (SS)

• a. Patients must have a histologically confirmed diagnosis of synovial sarcoma with a confirmation by the presence of a translocation between SYT on the X chromosome and SSX1, SSX2 or, SSX4 on chromosome 18 (may be presented in the pathology report as t (X; 18)).

• 19\. Myxoid/round cell liposarcoma (MRCLS)

• a. Patients must have histologically confirmed myxoid/round cell liposarcoma with a confirmation by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11) or t(12; 22) (q13;q12).

Locations
United States
Texas
MD Anderson Cancer Center
RECRUITING
Houston
Contact Information
Primary
John Livingston, MD
jalivingston@mdanderson.org
(713) 792-3626
Time Frame
Start Date: 2024-03-27
Estimated Completion Date: 2028-11-30
Participants
Target number of participants: 44
Treatments
Experimental: Dose escalation - Inpatient and Outpatient
Participants will be assigned to receive a dose level of NK cells based on when the participants joins the study. Up to 6 participants will be enrolled at each dose level. If no intolerable side effects are seen after the first 3-6, the next group of participants will get at higher dose. Up to 4 dose levels of NK cells will be tested. If the first dosing group shows intolerable side effects, a lower dose will be tested.
Sponsors
Leads: M.D. Anderson Cancer Center

This content was sourced from clinicaltrials.gov

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