CD56+CD3- NK Cells Following Allogeneic Stem Cell Transplantation

Study Overview
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Brief Summary
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The investigators propose a nonrandomized, Phase I study to assess the safety of infusion of NK cells that will be selected from sibling donors and infused to patients with hematological malignancies early following allogeneic stem cell transplantation.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (HSCT) is a very effective treatment for a number of hematological malignancies but relapse remains a major problem, especially in patients with high risk disease. Natural killer (NK) cells are immune cells that recognize and kill virally infected cells and tumor cells. NK cells are identified by the expression of the CD56 surface antigen and the lack of CD3. Their ability to kill tumor cells makes them promising to evaluate as effector cells for immunotherapy.

Official Title
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Safety and Toxicity of Escalating Doses of Adoptively Infused ex Vivo Selected CD56+CD3- NK Cells on Day 7 Following Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies.

Conditions
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Haematological Malignancies, Allogeneic Stem Cell Transplant, CD56+CD3- NK Cells

Intervention / Treatment
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* Procedure: Infusion of donor derived ex-vivo selected NK cells to patients after transplant
* Procedure: Haematology / Blood chemistry sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing an allogeneic HSCT from a sibling donor, as treatment for a hematological malignancy. The conditioning regimen, and in particular whether ablative or non ablative, will not be considered in the criteria for recruitment Patient and donor Age >18 years Patients and donors must have signed an informed consent form The donor must be willing and capable of donating lymphocytes for NK selection using apheresis techniques Donor must be fit to undergo leukapheresis Exclusion Criteria: Life expectancy < 3 months ECOG performance status 3 or 4 Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, life threatening cardiac arrhythmia Patients will not be eligible if they receive in vivo T depletion with ATG, ALG or campath-1H HIV-positive patients Psychiatric illness/social situations that would limit compliance with study requirements and ability to comprehend the investigational nature of the study and provide informed consent

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Infusion of donor derived ex-vivo selected NK cells to patients after transplant|Infusion of donor derived ex-vivo selected NK cells to patients after transplant|
|Procedure: Haematology / Blood chemistry sampling|Haematology / Blood chemistry sampling, collection of blood for ancillary lab research|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity donor CD56+CD3- NK cells | To evaluate the safety and toxicity of escalating doses of ex vivo selected donor CD56+CD3- NK cells, adoptively infused on day 7 following sibling allogeneic stem cell transplantation in patients with hematological malignancies. We will specifically look for the proportion of patients who develop infusion related toxicity. Toxicity will be defined as per the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). | Day 28 post NK cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor neutrophil and platelet engraftment | Donor neutrophil engraftment (Neut > 0.5 x10^9/L) and platelet engraftment (Plt > 20 x10^9/L) | Day 28 post stem cell infusion | 
| Rates of acute GVHD (grade 2-4) | Risk of acute GVHD | Day 100 post stem cell infusion | 
| Relapse rate | Relapse | 1 year post stem cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK, natural killer, immunotherapy, leukemia, hematological malignancies, stem cell transplantation, adoptive therapy