Acute Myeloid Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
Natural Killer cells, NK cells, Immunotherapy, haploidentical hematopoietic stem cell transplantation
Brief 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.
Interventions
OTHERNK-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.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, single center, open-label, single arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events including GvHD and infections. | 1 year following haplo HSCT | As defined by the CTCAE version 4.03 and the NIH Scoring of GvHD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 1 year following haplo HSCT | rejection. |
| 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 | — |
Countries
Switzerland
Contacts
Primary ContactMatyas Ecsedi, MD-PhD
Outcome results
None listed