This phase Ib trial tests the safety of natural killer (NK) cells with aldesleukin and vactosertib in treating patients with colorectal, gastric and esophageal cancers that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic) or hematologic cancers that has come back (relapsed) or does not respond to treatment (refractory). One of the ways that cancer grows and spreads is by avoiding the immune system. NK cells are immune cells that kill cancer cells, but are often malfunctioning in people with colorectal cancer and blood cancers. Natural killer cells are a type of white blood that are part of the body's defense system that kill cancer cells. NK cells in cancer patients are not able to kill cancer cells. Universal donor NK cells are cells from a healthy person. Chemotherapy before a donor NK cell transplant prepares the body by white blood cells so that they do not reject the NK cells. Aldesleukin activates donor NK cells. Vactosertib may activate donor NK cells. Giving NK cells from a healthy donor with aldesleukin and vactosertib may help to control cancer and tumor cells.
Additional locations may be listed on ClinicalTrials.gov for NCT05400122.
Locations matching your search criteria
United States
Ohio
Cleveland
Case Comprehensive Cancer CenterStatus: Active
Contact: Benjamin Kent Tomlinson
Phone: 216-844-0139
PRIMARY OBJECTIVES:
I. To determine the safety of NK feeder-expanded NK cells with aldesleukin (IL-2) and vactosertib.
II. To determine the persistence of donor NK cells at Day 7.
SECONDARY OBJECTIVES:
I. To assess clinical response at Day 28.
II. To determine the rate of persistence of donor NK cells collected from subject peripheral blood at Days 14, 21, and 28.
CORRELATIVE OBJECTIVES:
I. To determine if donor NK cells are trafficked to tumors in end of treatment biopsies.
II. To evaluate the activity of donor NK cells collected from subject peripheral blood at Day 7.
III. To characterize the immune repertoire changes after donor NK cell infusion in combination with IL-2 and vactosertib.
OUTLINE: This is a dose de-escalation study of aldesleukin being de-escalated.
Patients receive standard of care fludarabine phosphate intravenously (IV) over 30 minutes and cyclophosphamide IV over 60 minutes daily on days T-5 through T-3 prior to NK cell therapy. Patients then receive NK cell therapy IV over 250mL/hr on days T0 and T14, aldesleukin subcutaneously (SC) two or three times weekly for 4 weeks starting the same day as the first NK cell infusion, and vactosertib orally (PO) twice daily (BID) for five consecutive days weekly for 4 weeks. Patients also undergo bone marrow or tumor biopsy at baseline and after the end of treatment, and computed tomography scan (CT) and positron emission tomography (PET)/CT at baseline and day T28 and T100 and at 6 and 12 months, and collection of blood at baseline and days T0, T2, T4, T7, T14, T21, T28 and T100 and at 6 and 12 months.
After completion of study treatment, patients are followed up at 28 days, 100 days, 6 and 12 months after the first NK cell infusion.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorBenjamin Kent Tomlinson