Expanded Natural Killer Cells Following Haploidentical HSCT for AML/MDS

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Other: NK-DLI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, single center, open-label, single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NK-DLI<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natural Killer cells, NK cells, Immunotherapy, haploidentical hematopoietic stem cell transplantation