Expanded Natural Killer Cells Following Haploidentical HSCT for AML/MDS

A Phase I/II Single Center Study to Assess the Safety, Tolerability and Feasibility of Pre-emptive Immunotherapy With in Vitro Expanded Natural Killer Cells in Patients Treated With Haplo-HSCT for AML/MDS

The study examines the application of expanded natural killer cells (NK cells) following haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for AML or MDS. Haplo-HSCT is a preferred treatment option for patients with AML or MDS without a HLA-matched donor. With administration of cyclophosphamide post-transplant , the safety of the procedure is similar to a HSCT from a HLA-identical donor. Relapse of AML/MDS represents a serious problem following haplo-HSCT. NK cells are immune cells able to destroy tumor cells. Their potency has been established particularly in the setting of a haplo-HSCT. In the current study, study participants undergoing haplo-HSCT will receive expanded NK cells from their respective stem-cell donors following haplo-HSCT. The primary goal of the study is to establish the safety and feasibility of this approach. In addition, the activity of the NK cells will be examined.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Other: NK-DLI

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Matyas Ecsedi, MD-PhD; Phone Number: +41612652525; Email: matyas.ecsedi@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Matyas Ecsedi, MD-PhD; Phone Number: +41612652525; Email: matyas.ecsedi@usb.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patient:

• >18 years of age
• No HLA-matched related or unrelated donor available
• AML or MDS-EB with indication for a haplo-HSCT according to the guidelines of the University Hospital Basel Stem Cell Transplant Team
• Judged by the transplant physicians to have adequate organ function and no contraindications to haplo-HSCT
• Available related haploidentical donor
• Written informed consent

Donor:

• >18 years old, haploidentical parent, sibling or other relative
• Donor suitable for cell donation and apheresis according to standard criteria
• Written informed consent

Exclusion Criteria:

Patient:

• APL diagnosis
• Presence of relevant (mean fluorescence intensity >2000) donor-specific anti-HLA antibodies
• Pregnancy
• Necessity of immunosuppression apart from GvHD prophylaxis

Exclusion Criteria:

Donor:

• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NK-DLI; Preemptive immunotherapy with ex vivo expanded NK cells on days +10, +15 and +20 with increasing NK cell doses following haplo-HSCT.	Other: NK-DLI; Application of three infusions of ex vivo expanded NK cells on days +10, +15 and +20 with increasing NK cell doses (1x107/kg, 1x108/kg and the remaining cells up to 1x109/kg) following haplo-HSCT. Maximal cumulative T-cell dose is fixed at <1x105/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events including GvHD and infections.	As defined by the CTCAE version 4.03 and the NIH Scoring of GvHD.	1 year following haplo HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)		1 year following haplo HSCT
Incidence of AML/MDS-EB complete morphological and molecular remission (CR) at day + 30, + 90, +180 and 1 year post allo-HSCT	rejection.	1 year following haplo HSCT
Incidence of graft rejection		1 year following haplo HSCT
Number of NK cells given per kg body weight		30 days following haplo-HSCT
Number of NK-DLI infusions applied		30 days following haplo-HSCT

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Jakob Passweg, Prof. MD, University Hospital Basel, Basel Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 30, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; NK cells; haploidentical hematopoietic stem cell transplantation; Natural Killer cells
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
• Other Study ID Numbers: Haplo-NK-DLI for AML/MDS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No