Safety Study Looking at the Use of a Natural Killer Cell Line Against Hematological Malignancies

Lymphoma Clinical Trial

Official title:

A Dose Escalation Study of NK-92 Cell Infusions in Patients With Hematological Malignancies in Relapse After Autologous Stem Cell Transplantation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990717
• Other study ID #: CTP04.NK92.01
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: June 21, 2016
• Start date: March 2005
• Est. completion date: July 2012

Study information

• Verified date: June 2016
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out how many irradiated natural killer (NK) cells can be safely given to patients with cancer that has recurred after an autologous stem cell transplant, and to see what effects (good and bad) it has on the patient and their cancer. This research is being done because currently, there is no cure or effective treatment for blood-borne cancers when it has come back after an autologous stem cell transplant.

Description:

Patients with hematological malignancies such as acute leukemia, lymphoma, Hodgkin's disease and myeloma, are generally treated initially with chemotherapy, radiotherapy or a combination of both. High dose therapy and autotransplantation are often utilized in the management of such patients, either as part of initial therapy or for treatment of relapsed disease. When a patient's cancer relapses after transplantation, the prognosis is dismal. Therapeutic options are usually limited to palliative chemotherapy and/or local radiation, and for persons with excellent performance status experimental treatments are considered on an ad hoc basis.

Much interest in the last decade has focused on the role of cellular and immunotherapy in this setting. Cancer vaccines and the administration of adoptive cellular and immunotherapy have the theoretical advantage of being non cross-reactive with previous treatments (such as radiotherapy and chemotherapy) and are currently under investigation using a variety of methodologies. NK cells comprise roughly 15% of all lymphocytes in the peripheral blood. They normally function as part of the innate immune system, which provides the body's initial response to infection and malignancy. However, patients with malignancies frequently have impaired NK cell function, as evidenced by reduced in vitro proliferative responses and reduced cytotoxic activity. The infusion of an irradiated NK cell line is appealing as it is a source of cells that can be expanded to therapeutic quantities, and retains anti-tumor activity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hematological malignancy (with prior histological confirmation) that has relapsed after an autologous stem cell transplant and for which there is no known curative or standard therapy. Specific hematological malignancies include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma.

• Assessable disease as measured by clinical, radiological or bone marrow examinations

• ECOG performance status 0, 1 or 2

• Age = 18 years

• Life expectancy greater than 12 weeks

• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and University Human Experimentation Committee requirements.

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: Absolute granulocytes = 0.5 x 109/L, Platelets = 50 x 109/L, Serum creatinine < 1.5 x upper limit of normal, Bilirubin < 1.5 x upper limit of normal, AST/ALT = 3 x upper limit of normal, Calcium < 1.25 x upper limit of normal. These tests must be conducted within 7 days prior to registration.

• Must be able to come to Princess Margaret Hospital, Toronto, Canada for treatment and follow-up.

Exclusion Criteria:

• Pregnant or nursing women may not participate.

• Men or women of reproductive potential may not participate unless they agree to practice an effective method of birth control. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to registration.

• Concurrent treatment, or treatment within 28 days of registration with other experimental drugs or anticancer therapy. Exceptions to this are: Patients who are receiving or who have received radiation therapy less than four weeks prior to study entry will not be excluded providing the volume of bone marrow treated is less than 10% and that the patient has measurable disease outside the radiation field. Hydroxyurea may be administered to patients with high white cell counts but must be discontinued at least 48 hours prior to the NK-92 cell infusions

• Patients with CNS involvement

• Known HIV, HBV or HCV infection

• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular events within 3 months of registration, or psychiatric or emotional disorders.

• Patients with hypersensitivity or previous severe reactions to Allopurinol, Acetominophen or Benadryl and all available alternative medications.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Lymphoma
• Myeloma

Intervention

Biological:
• NK-92 cells
Cells are administered as an intravenous infusion over one hour on days 1, 3 and 5 of each cycle of treatment. Patients can receive up to 6 cycles, which are administered monthly. Cell dosage is as follows: Level I: 1x10^9 cells/m^2 Level II: 3x10^9 cells/m^2 Level III: 5x10^9 cells/m^2

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994 Apr;8(4):652-8. — View Citation

Klingemann HG, Martinson J. Ex vivo expansion of natural killer cells for clinical applications. Cytotherapy. 2004;6(1):15-22. — View Citation

Maki G, Tam YK, Berkahn L, Klingemann HG. Ex vivo purging with NK-92 prior to autografting for chronic myelogenous leukemia. Bone Marrow Transplant. 2003 Jun;31(12):1119-25. — View Citation

Tam YK, Miyagawa B, Ho VC, Klingemann HG. Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J Hematother. 1999 Jun;8(3):281-90. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine if there are any dose limiting toxicities to this therapy, as well as the maximum tolerated dose.		Day 1, 3, and 5 of each cycle	Yes
Secondary	Document any preliminary efficacy information from the NK-92 cell infusion.		6 months	No
Secondary	Assess any immune response directed against the infused NK-92 cells.		28 days after each cycle	Yes
Secondary	Determine kinetics of infused NK92 cells.		Pre-infusion, 15 min, 2h, 6h, 24h, 48h, 168h post infusion	No