NCT04220684

Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML

A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-shelf, Third-party Natural Killer Cells (KDS-1001) for the Induction of Relapsed/Refractory Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Sumithira Vasu · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety of adoptive NK cell therapy using membrane-bound interleukin-21 (mbIL21)-expanded, off-the-shelf, third-party donor-derived NK cells in patients with relapsed/refractory acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. Estimate the complete response (CR, CR with incomplete hematologic recovery \[CRi\] \& morphologic leukemia-free state \[MLFS\]). II. Estimate the median relapse free survival. III. Estimate the median time to neutrophil and platelet count recovery. IV. Estimate the median duration of remission. V. Estimate the incidence of infectious complications. VI. Estimate percentage of patients receiving this regimen who are rendered transplant-eligible. CORRELATIVE OBJECTIVES: I. Determine the persistence of ex-vivo expanded, off-the-shelf, third-party NK cells. II. Characterize in vivo expansion of third-party NK cells and if it differs based on the conditioning regimen as defined by NK chimerism assay. III. Determine the immunophenotype and function of expanded cells. IV. Chimerism analysis in patients who have had post-transplant relapses. OUTLINE: This is a dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells. INDUCTION: Patients receive fludarabine intravenously (IV) and cytarabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity. COHORT II: Patients who are \>= 60 years old, unable/unwilling to tolerate intensive chemotherapy, or disease insensitive to cytarabine (tp53, TET2 mutations) receive fludarabine IV on days -5 to -2 and decitabine IV on days -6 to -2 in the absence of disease progression or unacceptable toxicity. All patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells via infusion on days 0, 2, 4, 7, 9, and 11. After completion of study treatment, patients are followed up to day 56.

Conditions

• Allogeneic Stem Cell Transplant Recipient
• Blasts 10 Percent or More of Bone Marrow Nucleated Cells
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine Hydrochloride	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Membrane-bound Interleukin-21-Expanded Haploidentical Natural Killer Cells	Given via infusion

Timeline

• Start date: 2020-06-11
• Primary completion: 2024-10-22
• Completion: 2024-10-22
• First posted: 2020-01-07
• Last updated: 2026-01-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study