Human Leukocyte Antigen (HLA) Class I Haplotype Mismatched Natural Killer Cell Infusions - Full Text View

Sponsor:	Tufts Medical Center
Collaborator:	University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00660166

Purpose

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.

Condition	Intervention	Phase
Lymphoma Myeloma Leukemia	Biological: NK-Cell Infusion	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	HLA Class I Haplotype Mismatched Natural Killer Cell Infusions After Autologous Stem Cell Transplant for Hematological Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia Lymphoma

U.S. FDA Resources

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:

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. [ Time Frame: 58 days post infusion of allogeneic NK-cells ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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

Estimated Enrollment:	12
Study Start Date:	April 2006
Estimated Study Completion Date:	November 2013
Estimated Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Biological: NK-Cell Infusion 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.

Arms

Assigned Interventions

Experimental: 1

Biological: NK-Cell Infusion

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.

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.

Eligibility

Ages Eligible for Study:	13 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660166

Locations

United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111

Sponsors and Collaborators

Tufts Medical Center

University of Minnesota - Clinical and Translational Science Institute

Investigators

Principal Investigator:

Hans Klingemann, MD, PhD

Tufts Medical Center

More Information

Additional Information:

Cancer Center at Tufts Medical Center This link exits the ClinicalTrials.gov site

Publications:

Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells. Horm Metab Res. 2008 Feb;40(2):122-5.

Klingemann HG. Natural killer cell-based immunotherapeutic strategies. Cytotherapy. 2005;7(1):16-22. Review.

Responsible Party:	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00660166 History of Changes
Other Study ID Numbers:	Allogeneic NKCell post ABMT
Study First Received:	April 11, 2008
Last Updated:	October 31, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Tufts Medical Center:

Natural killer cells
autologous stem cell transplant
immunotherapy

Additional relevant MeSH terms:

Leukemia
Lymphoma
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on February 09, 2012