Clinical trial NCT00660166: Human Leukocyte Antigen (HLA) Class I Haplotype Mismatched Natural Killer Cell Infusions
Official title: HLA Class I Haplotype Mismatched Natural Killer Cell Infusions After Autologous Stem Cell Transplant for Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Myeloma
Leukemia
Keywords: Natural killer cells
autologous stem cell transplant
immunotherapy
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: University of Minnesota
First posted: 2008-04-17
Enrollment: 13
Sex: ALL
Minimum age (years): 13
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 58 days post infusion of allogeneic NK-cells
Secondary outcomes:
measure: Duration of donor NK cells in the recipient's blood
timeFrame: 58 days post infusion of allogeneic NK-cells
measure: Patient survival at 100 days and at one year post treatment (all cause mortality)
timeFrame: 100 days and one year post treatment
measure: Occurrence of new cancer during the first year post infusion of allogeneic NK-cells
timeFrame: One year post infusion of allogeneic NK-cells
measure: Documented systemic infections during the first 30 days post infusion of allogeneic NK-cells.
timeFrame: 30 days post infusion of allogeneic NK-cells
measure: Occurrence of other possible NK-infusions related complications such as,fever, capillary leak syndrome and/or allergic reaction.
timeFrame: 58 days post infusion of allogeneic NK-cells
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Hans Klingemann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells. Horm Metab Res. 2008 Feb;40(2):122-5. doi: 10.1055/s-2007-1004576.
citation: Klingemann HG. Natural killer cell-based immunotherapeutic strategies. Cytotherapy. 2005;7(1):16-22. doi: 10.1080/14653240510018000.