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

Condition(s) targeted: Lymphoma; Myeloma; Leukemia

Intervention: NK-Cell Infusion (Biological)

Phase: Phase 1

Status: Recruiting

Sponsored by: Tufts Medical Center

Official(s) and/or principal investigator(s):
Hans Klingemann, MD, PhD, Principal Investigator, Affiliation: Tufts Medical Center

Overall contact:
Hans Klingemann, MD, PhD, Phone: (617) 636-2520, Ext: 6-2520, Email: hklingemann@tuftsmedicalcenter.org

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.

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

Study design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study

Primary outcome: 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.

Secondary outcome:

Duration of donow NK cells in the recipient's blood

Patient survival at 100 days and at one year post treatment (all cause mortality)

Occurrence of new cancer during the first year post infusion of allogeneic NK-cells

Documented systemic infections during the first 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.

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.

Minimum age: 13 Years. Maximum age: 70 Years. Gender(s): Both.

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.

Hans Klingemann, MD, PhD, Phone: (617) 636-2520, Ext: 6-2520, Email: hklingemann@tuftsmedicalcenter.org

Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting
Hans Klingemann, MD, PhD, Phone: 617-636-2520, Ext: 6-2520, Email: hklingemann@tuftsmedicalcenter.org
Carrie Grodman, RN, Phone: (617) 636-2682, Ext: 6-2682, Email: cgrodman@tuftsmedicalcenter.org
Andreas Klein, MD, Sub-Investigator
Kellie Sprague, MD, Sub-Investigator
David McKenna, MD, Sub-Investigator
Howard Grodman, MD, Sub-Investigator
Lawrence Wolfe, MD, Sub-Investigator
Richard A. Van Etten, MD, PhD, Sub-Investigator
Kenneth B. Miller, MD, Sub-Investigator

Cancer Center at Tufts Medical Center

Starting date: April 2007
Ending date: November 2009
Last updated: October 13, 2009