Haploidentical Stem Cell Transplant With or Without NK Cell Infusion in AML and MDS

Study Overview
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Brief Summary
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Relapse after an allogeneic hematopoietic stem cell transplantation (HSCT) is high in patients with advanced AML, in the 50% range. NK cells have been shown to possess significant anti-leukemic activity and may be used to reduce the incidence of relapse in patients with advanced AML. Investigators hypothesize that the administration of a purified boost of NK cells on day +7 post HSCT, will reduce the incidence of relapse from the current 50% to 25%. In a phase III multicenter clinical study, 116 patients will be randomized to receive or not a boost of donor NK cells on day +7 post-HSCT. The first 10 patients in the experimental arm will be analyzed for toxicity. The stopping rule will be a transplant related mortality of more than 50% in the first 20 patients who received NK cells.

Official Title
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Haploidentical Stem Cell Transplantation With or Without NK Cell Infusion in Refractory/Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome:The BigEMINy Study

Conditions
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Acute Myeloid Leukemia, Myelodysplasia

Intervention / Treatment
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* Biological: Haplo SCT with NK cells
* Biological: Haplo SCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AML or MDS Patients not in remission at the time of transplant Age 18-75 ECOG performance status <2 Availability of a family HLA haploidentical donor, eligible to donate both marrow cells and unstimulated lymphocytes (1 apheresis procedure at day +7) . Exclusion Criteria: Positive serologic markers for human immunodeficiency virus (HIV) Acute hepatitis B virus (HBV) or acute hepatitis C virus (HCV) infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haplo-stem cell transplant followed by NK infusion<br>Haplo stem cell transplant (from bone marrow or apheresis) is followed by a haplo-NK cell infusion (target dose ≥1*106/kg b.w.) at day 7. Unstimulated haplo-NK cells are collected through apheresis Mononuclear cells are then subjected to a preliminary negative selection of CD3+ cells and to a subsequent positive selection of CD56+ cells. CD3 negative/CD56 positive cells are infused | Biological: Haplo SCT with NK cells<br>* Patients in this arm receive haplo-SCT followed by one boost of NK cells one/two weeks after the transplant. Lymphocyte are collected by apheresis from the donor one-two weeks after BM harvest. CD3 negative/CD56 positive cells are selected by immunomagnetic columns (other lymphocytes are stored to be used as DLI)<br>* Other names: haplo SCT followed by NK cell infusion;|
| Active Comparator: Haplo-stem cell transplant<br>Patients in this arm receive standard haplo stem cell transplant (from bone marrow or apheresis) transplant without subsequent NK cell infusion. | Biological: Haplo SCT<br>* Patients in this arm receive a standard haplo-SCT. All administerd therapies are the same as in other arm, except for the NK cell boost..<br>* Other names: Standard haplo SCT without subsequent NK cell boost.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukemia relapse | Cumulative incidence of leukemia relapse. | 1 year after bone marrow transplant |