In Vitro Expanded Autologous Invariant Natural Killer Cells in Cancer

NCT ID: NCT00631072

Last Updated: 2017-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2015-04-30

Brief Summary

The purpose of this research study is to determine whether we can purify and grow a population of cells from the participants blood (iNKT cells) and then safely give them back to the participant in increased numbers, and whether these cells will then stimulate the bodies own immune response against the cancer. These iNKT cells have been used in laboratory studies and information from these and other research studies suggest that increasing the number of these cells in the blood can stimulate the immune response against tumors.

Detailed Description

• The first step in the study will be to collect iNKT cells from the participants peripheral blood. For this procedure an intravenous catheter will be used to remove the blood. The white blood cells will be removed from the blood and the red blood cells and plasma will be returned to the participant (leukopheresis).
• We will then purify the iNKT cells from these collected white blood cells, and will grow them in culture plates in the lab under strictly controlled sterile conditions. This can take 4-6 weeks.
• If we are successful in growing the iNKT cells to large enough numbers, they will be divided into 3 equal doses. Participants will receive one dose of these cells by intravenous infusion every 2 weeks or days 1, 15 and 29. A blood sample will be taken immediately before each infusion, and at 1 and 4 hours after each infusion. Participants will be asked to return for blood samples on day 2, 3, 4 and 8 after infusion.
• The initial group of 3-6 participants will not receive any other therapy with the iNKT cell infusions. However, the subsequent group of 6 patients will in addition receive GM-CSF, which can further stimulate the immune system and may increase the effects of the iNKT cells. This medication is administered by subcutaneous injection and will be given daily for 10 days beginning the day of the second and third infusion.
• Participants will be on this research study for about 14 weeks, which includes the time for the cell purification and culture, treatment, and follow-up observation.

Conditions

Malignant Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GM-CSF +INKT

INKT will be administered in 3 equal doses by intravenous infusion on days 1, 15 and 29.

GM-CSF will be given subcutaneously once daily for 10 days beginning the second day of the second and third infusion

Group Type: OTHER

INKT

Intervention Type: BIOLOGICAL

Administered in 3 equal doses by intravenous infusion on days 1, 15 and 29.

GM-CSF

Intervention Type: DRUG

Given subcutaneously once daily for 10 days beginning the second day of the second and third infusion

Interventions

INKT

Administered in 3 equal doses by intravenous infusion on days 1, 15 and 29.

Intervention Type: BIOLOGICAL

GM-CSF

Given subcutaneously once daily for 10 days beginning the second day of the second and third infusion

Intervention Type: DRUG

Other Intervention Names

In vitro expanded autologous invariant natural killer T cells

Eligibility Criteria

Inclusion Criteria

• Stage IV melanoma
• ECOG Performance Status 0-1
• Estimated life expectancy of 6 months or greater
• 18 years of age or older
• Adequate renal, hepatic and hematological function as outlined in protocol
• Adequate pulmonary and cardiac function as outlined in protocol
• Prior therapies must be discontinued at least 4 weeks prior to the leukopheresis to obtain iNKT cells. This does not include palliative surgery or radiation therapy, which may be used prior to leukopheresis or during the interval between leukopheresis and iNKT cell reinfusion
• Melanoma patients must not have brain metastases based on a negative MRI obtained within 4 weeks prior to screening, and must not have a history of brain metastases
• No other significant medical, surgical or psychiatric condition that, in the judgment of the PI, would interfere with compliance to the protocol regimen

Exclusion Criteria

• Pregnant or nursing women
• Active systemic infection, positive HIV, HBV, or HCV serology, or immune deficiency disease
• Autoimmune disease that currently requires systemic therapy with immunosuppressive agents
• Known hypersensitivity to GM-CSF or DMSO
• Other active malignancy other than squamous cell or basal cell of the skin

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steven Balk, MD

Steven Balk, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Balk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

F. Stephen Hodi, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

06-432

Identifier Type: -

Identifier Source: org_study_id