A Phase I Trial of Alloreactive Cell Infusion Following Transplantation of Haplotype Cells in Patients With Myeloid Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximum tolerated dose of alloreactive NK cells that can be transfused following stem cell transplant.

Official Title
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A PHASE I TRIAL OF ALLOREACTIVE NK CELLS INFUSION FOLLOWING TRANSPLANTATION OF HAPLOTYPE MISMATCHED, KIR MISMATCHED HIGHLY PURIFIED CD34 CELLS IN PATIENTS WITH ADVANCED OR REFRACTORY MYELOID MALIGNANCIES

Conditions
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Leukemia, Myeloid, Acute, Leukemia, Lymphoid, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic

Intervention / Treatment
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* Device: CliniMACS CD34 Reagent System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically documented AML, ALL, MDS, CML, Identification of haploidentical donor LVEF > 45% corrected DLCO > 50% predicted Serum Creatinine <= 2 mg/dL Bilirubin < 2 x ULN AST, ALT < 2 x ULN Age ≤ 65 years Performance Status 0-1 Exclusion Criteria: Patients relapsing <6 months after autologous SCT are not eligible. Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection No HIV disease Non-pregnant and non-nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alloreactive NK cell infusion<br>Escalating doses of alloreactive NK cells. | Device: CliniMACS CD34 Reagent System<br>* Alloreactive NK cells will be purified by a two-step immunomagnetic selection (CD3 depletion followed by CD56 selection) using the CliniMACS device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the maximum-tolerated dose (MTD) of highly-purified alloreactive NK cells infused following haplotype-mismatched, KIR ligand-mismatched transplants in patients with refractory hematological malignancies. |  | through Day 128 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess toxicity associated with the infusion of alloreactive NK cells |  | through Day 128 | 
| Assess the risk of acute and chronic GvHD following infusion of alloreactive NK cells. |  | through Day 128 | 
| Assess the feasibility of multiple harvesting and purifying NK cells to the relatively high-doses. |  | through Day 128 | 
| Describe the frequency and type of infections occurring within the first year following transplantation. |  | through Day 128 | 
| Describe immune reconstitution following transplantation. |  | through Day 128 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloid Malignancies, Bone Marrow Transplant, AML, ALL, MDS, CML