Expanded Natural Killer Cells Following Haploidentical HSCT for AML/MDS

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03300492
• Other study ID #: Haplo-NK-DLI for AML/MDS
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 12, 2018
• Est. completion date: January 31, 2026

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Matyas Ecsedi, MD-PhD
• Phone: +41612652525
• Email: matyas.ecsedi[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Intervention

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.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free survival (PFS)		1 year following haplo HSCT
Secondary	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
Secondary	Incidence of graft rejection		1 year following haplo HSCT
Secondary	Number of NK cells given per kg body weight		30 days following haplo-HSCT
Secondary	Number of NK-DLI infusions applied		30 days following haplo-HSCT