Human Leukocyte Antigen (HLA) Class I Haplotype Mismatched Natural Killer Cell Infusions

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to examine the safety of infusing escalated doses of allogeneic (from a relative of the patient), enriched natural killer (NK) cells after autologous (from the patient) stem cell transplantation. The hypothesis is that the infusion of these NK cells early after an autologous stem cell transplant will help to eliminate and eradicate any residual cancerous cells that remain in the body and may have survived the chemotherapy or radiation.

Detailed Description
-----------------
Natural killer cells are blood cells that are responsible for eliminating cancer cells especially when there are only a few. It has been shown that NK cells coming from a mismatched person (a relative) have a better chance than the patient's own NK cells to recognize and kill cancer cells. These cells will be collected from the blood of a parent, child or sibling and after preparation in the laboratory, will be given to the patient early after an autologous stem cell transplantation like a blood or platelet transfusion. A person who has been diagnosed with a blood tumor and received an autologous stem cell transplant has the chance of his/her cancer coming back. This study uses NK cells obtained from a relative to prevent disease recurrence by potentially eliminating and eradicating any residual cancerous cells.

Official Title
-----------------
HLA Class I Haplotype Mismatched Natural Killer Cell Infusions After Autologous Stem Cell Transplant for Hematological Malignancies

Conditions
-----------------
Lymphoma, Myeloma, Leukemia

Intervention / Treatment
-----------------
* Biological: NK-Cell Infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who have undergone an autologous stem cell transplant for the following diseases: Acute Myeloid Leukemia Non-Hodgkin's Lymphoma Hodgkin's Disease Multiple Myeloma Age 13 - 70 years old Able to give informed consent Hepatic and renal function: bilirubin less than or equal to 2x normal limits, AST and ALT less than or equal to 2x normal limits, serum creatinine less than or equal to 1.5x normal ECOG Performance Status less than or equal to 1 (at planned time of transplantation) Patients with no active infection Exclusion Criteria: Patients who have not recovered sufficiently from the side effects of the autologous transplant (i.e. have > grade 2 toxicity in any organ system) Patients who have insufficient engraftment parameters according to the following criteria: WBC < 2,500 /mm3 and platelets < 50,000/mm3 Radiation therapy, chemotherapy, or immunotherapy beginning one week before NK-cell infusion and lasting 2 weeks after NK-cell infusion. Intrinsic impaired organ function (as stated above). Physical or psychiatric conditions that in the estimation of the PI or designee place the patient at high-risk of toxicity or non-compliance. Uncontrolled, life-threatening infections at the time of infusion. Concurrent treatment with corticosteroids and/or other immuno-suppressive drugs.

Ages Eligible for Study
-----------------
Minimum Age: 13 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: NK-Cell Infusion<br>* The infusion of natural killer (NK) cells will be performed in the Infusion Center at New England Medical Center. The NK cells will be given to the subject intravenously (into a vein). In addition, a balanced salt solution will be infused beginning about two hours prior to and continuing for two hours after the infusion of NK cells to keep the fluid level in the body well balanced. The subject will also receive Benadryl by injection 15-30 minutes prior to infusion to counteract and prevent any unwanted allergic side effects. The subject will be observed for any side effects during this time. If the subject feels well, he/she can go home. However, there may be a requirement to keep him/her overnight.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| An evaluation of general safety will be undertaken: · Number of systemic clinical and biological adverse events occurring during the study. · Number of patients who prematurely discontinued study treatment for reasons linked to the general safety. |  | 58 days post infusion of allogeneic NK-cells | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of donor NK cells in the recipient's blood |  | 58 days post infusion of allogeneic NK-cells | 
| Patient survival at 100 days and at one year post treatment (all cause mortality) |  | 100 days and one year post treatment | 
| Occurrence of new cancer during the first year post infusion of allogeneic NK-cells |  | One year post infusion of allogeneic NK-cells | 
| Documented systemic infections during the first 30 days post infusion of allogeneic NK-cells. |  | 30 days post infusion of allogeneic NK-cells | 
| Occurrence of other possible NK-infusions related complications such as,fever, capillary leak syndrome and/or allergic reaction. |  | 58 days post infusion of allogeneic NK-cells | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Natural killer cells, autologous stem cell transplant, immunotherapy