Trials / Suspended

SuspendedNCT05400122

Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer

A Phase Ib Study to Evaluate Safety and Persistence of ex Vivo Expanded Universal Donor NK Cells in Combination With IL-2 and TGFbeta Receptor I Inhibitor Vactosertib in Patients With Locally Advanced/Metastatic Colorectal Cancer, Gastric/Esophageal Cancer, and Relapsed/Refractory Hematologic Malignancies

Status: Suspended
Phase: Phase 1
Study type: Interventional
Enrollment: 12 (estimated)

Sponsor: David Wald · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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. A safe way to give people with colorectal cancer and blood cancers fresh NK cells from a healthy donor has recently been discovered. The purpose of this study is to show that using two medicines (vactosertib and IL-2) with NK cells will be safe and will activate the donor NK cells. NK cells and vactosertib are experimental because they are not approved by the Food and Drug Administration (FDA). IL-2 (Proleukin®) has been approved by the FDA for treating other cancers, but the doses used in this study are lower than the approved doses and it is not approved to treat colorectal cancer or blood cancers.

Detailed description

The goal of our study is to demonstrate that natural killer (NK) cells from non- HLA-matched donors can be safely infused into patients with colorectal cancer, patients with gastric or esophageal cancer, and patients with relapsed/refractory hematologic malignancies in combination with IL-2 and the oral TGFβ receptor I inhibitor vactosertib to improve the persistence of donor NK cells.

Conditions

Interventions

Type	Name	Description
DRUG	Vactosertib	Vactosertib is a highly selective, potent inhibitor of the protein serine/threonine kinase activity of transforming growth factor (TGF)-β receptor type 1 (TGFBR1; also known as activin receptor-like kinase 5 \[ALK5\]). Vactosertib inhibits the phosphorylation of the ALK5 substrates Smad2 and Smad3, as well as the intracellular signaling of TGF-β.
DRUG	Fludarabine Phosphate	Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoroara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis.
DRUG	Cyclophosphamide	Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity.
DRUG	IL-2	Proleukin® (aldesleukin) has been shown to possess the biological activities of human native interleukin-2. In vitro studies performed on human cell lines demonstrate the immunoregulatory properties of Proleukin, including: a) enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines; b) enhancement of lymphocyte cytotoxicity; c) induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and d) induction of interferon-gamma production. The in vivo administration of Proleukin in animals and humans produces multiple immunological effects in a dose dependent manner. These effects include activation of cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia, and the production of cytokines including tumor necrosis factor, IL-1 and gamma interferon. In vivo experiments in murine tumor models have shown inhibition of tumor growth
DRUG	Natural Killer Cells	Adoptive NK cell therapy has demonstrated the potential for cancer immunotherapy in various malignancies with particular potential in hematologic malignancies including acute myeloid leukemia (AML), and colon cancer \[14, 19-23\]. This therapeutic approach is extremely well tolerated in patients even when massive numbers of cells are utilized (\~109 NK cells/kg). In fact, studies suggest that high doses of NK cells are not only well tolerated but have potential to lead to higher levels of efficacy.

Timeline

Start date: 2022-09-09
Primary completion: 2025-12-31
Completion: 2026-06-01
First posted: 2022-06-01
Last updated: 2025-11-12

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05400122. Inclusion in this directory is not an endorsement.