Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
Dr. Armand Keating, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00990717
First received: October 6, 2009
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Myeloma
Hodgkin's Disease
Biological: NK-92 cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Study of NK-92 Cell Infusions in Patients With Hematological Malignancies in Relapse After Autologous Stem Cell Transplantation.

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Determine if there are any dose limiting toxicities to this therapy, as well as the maximum tolerated dose. [ Time Frame: Day 1, 3, and 5 of each cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Document any preliminary efficacy information from the NK-92 cell infusion. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Assess any immune response directed against the infused NK-92 cells. [ Time Frame: 28 days after each cycle ] [ Designated as safety issue: Yes ]
  • Determine kinetics of infused NK92 cells. [ Time Frame: Pre-infusion, 15 min, 2h, 6h, 24h, 48h, 168h post infusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: March 2005
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NK-92 cells
Preparation of irradiated NK-92 cells suspended in a saline and plasma solution. NK-92 working cell bank was established from a master cell bank supplied by Conkwest Inc. (San Diego CA).
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990717

Contacts
Contact: Jan McCrae, RN 416-946-4500 ext 5136 jan.mccrae@uhn.on.ca

Locations
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Armand Keating, MD         
Sub-Investigator: Michael Crump, MD         
Sub-Investigator: Vikas Gupta, MD         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Armand Keating, MD Princess Margaret Hospital, Canada
  More Information

Publications:
Responsible Party: Dr. Armand Keating, Clinical Studies Resource Centre Member / Senior Scientist, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00990717     History of Changes
Other Study ID Numbers: CTP04.NK92.01
Study First Received: October 6, 2009
Last Updated: July 14, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
natural killer cells
leukemia
lymphoma
myeloma
Hodgkin's disease
cell therapy

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014