Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00515957
Status:
WITHDRAWN
Last Update Posted:
2012-04-16
First Post:
2007-08-10
Brief Title:
Study of LMP1- and LMP2- Specific Cytotoxic T-Lymphocytes CTL
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Administration of LMP1- and LMP2-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody Administration to Patients With EBV-Positive Nasopharyngeal Carcinoma
Status:
WITHDRAWN
Status Verified Date:
2012-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DELLA
Brief Summary:
In this study NPC patient will receive 4 days of treatment with CD45 antibody followed by one dose of LMP1- and LMP2-CTL From this we can learn if treating the patient first with the CD45 antibody will also let LMP1- and LMP2-CTL we give grow better In addition we will find out if LMP1- and LMP2-CTL are safe and have enhanced anti-tumor activity in comparison to standard EBV-CTL
This study aims to determine the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes CTL in combination with CD45 monoclonal antibody MAb in patients with EBV-positive nasopharyngeal carcinoma NPC
And to obtain information on the expansion persistence and anti-tumor effects of autologous LMP1- and LMP-2 specific CTL given after lymphodepletion with CD45 MAb in patients with EBV-positive NPC
This study aims to determine the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes CTL in combination with CD45 monoclonal antibody MAb in patients with EBV-positive nasopharyngeal carcinoma NPC
And to obtain information on the expansion persistence and anti-tumor effects of autologous LMP1- and LMP-2 specific CTL given after lymphodepletion with CD45 MAb in patients with EBV-positive NPC
Detailed Description:
While patients with nasopharyngeal carcinoma NPC may be cured by chemotherapy and radiotherapy the outlook for patients who are resistant to this treatment or who relapse is poor Almost all patients with undifferentiated nasopharyngeal carcinoma have the EBV virus in their tumors which may be a target for immunotherapy approaches We have successfully used specialized immune system cells grown in the laboratory and trained to recognize and kill EBV infected cells EBV-specific cytotoxic T-lymphocytes EBV-CTL to prevent and treat another type of cancer called post transplant lymphoma that occurs after bone marrow transplant In post transplant lymphoma the tumor cells have 9 proteins made by EBV on their surface However in nasopharyngeal carcinoma that develops in patients with a normal immune system the tumor cells only express 2 EBV proteins that are much harder for the immune system to recognize In a previous study we made EBV-CTL that recognized all 9 proteins and gave them to patients with NPC For patients without evidence of active disease at the time of therapy there disease remains in remission For those patients with active disease at the time they received CTL some patients had a partial response to this therapy and only three patients had a complete response We think the main reason for this is that many of the T cells reacted with EBV proteins that were not on the tumor cells and the other is that the infused T cells have not enough space to grow
The two EBV proteins present on NPC tumor cells that are good targets for T-cell therapies are called LMP1 and LMP2 We are therefore planing to generate T cells specific for LMP1 and LMP2 and infuse these cells into NPC patients To make LMP1- and LMP2-CTL we have obtained blood from the patients and grown special type of cell called a dendritic cell DC and EBV infected lymphoblastoid cells LCL We have then transferred an adenovirus vector that carries the LMP1 and LMP2 gene into the DC and the LCL These DC and LCL are then treated with radiation so they cannot grow and are used to stimulate and expand LMP1- and LMP2-CTL This stimulation trains the T cells to kill cancer cells with LMP1 and LMP2 on their surface
To create space for EBV-CTL growth after infusion in NPC patients we have already used a special protein called a CD45 antibody which removes for a short period of time most of the patients T cells The preliminary results of this study is encouraging the use of the CD45 antibody is safe and we observed enhanced EBV-CTL growth after infusion In addition all patients who has EBV-CTL growth had clinical responses
We and others have demonstrated the feasibility of CTL therapy for EBV-positive NPC in immunocompetent patients providing preliminary evidence of anti-tumor activity of EBV-CTL in this patient population Not all patients responded however suggesting the need for further improvement We propose that CTL failure can be overcome by increasing the specificity of the infused CTL product That is infusion of CTL specific for LMP1 and LMP2 will produce greater clinical benefit than EBV-specific CTL The rationale for this approach is straight forward EBV-specific CTL lines generated by standard methods are dominated by T-cell clones not reactive to the subdominant EBV proteins LMP1 and LMP2 expressed in NPC We also propose that the failure of adoptively transferred CTL to measurably expand in the peripheral blood of NPC patients is a consequence both of lymphoid homeostasis in these lympho-replete patients and of the inhibitory T-cell infiltrate at the sites of disease We will therefore use monoclonal antibodies targeting the CD45 antigen CD45 MAbs to lymphodeplete NPC patients prior to the infusion of EBV-specific CTL Preliminary results indicate that CD45 MAb depletion can augment CTL expansion and that such expansion is associated with a higher disease response rate We will confirm and extend these promising new data in this Phase I clinical trial
The two EBV proteins present on NPC tumor cells that are good targets for T-cell therapies are called LMP1 and LMP2 We are therefore planing to generate T cells specific for LMP1 and LMP2 and infuse these cells into NPC patients To make LMP1- and LMP2-CTL we have obtained blood from the patients and grown special type of cell called a dendritic cell DC and EBV infected lymphoblastoid cells LCL We have then transferred an adenovirus vector that carries the LMP1 and LMP2 gene into the DC and the LCL These DC and LCL are then treated with radiation so they cannot grow and are used to stimulate and expand LMP1- and LMP2-CTL This stimulation trains the T cells to kill cancer cells with LMP1 and LMP2 on their surface
To create space for EBV-CTL growth after infusion in NPC patients we have already used a special protein called a CD45 antibody which removes for a short period of time most of the patients T cells The preliminary results of this study is encouraging the use of the CD45 antibody is safe and we observed enhanced EBV-CTL growth after infusion In addition all patients who has EBV-CTL growth had clinical responses
We and others have demonstrated the feasibility of CTL therapy for EBV-positive NPC in immunocompetent patients providing preliminary evidence of anti-tumor activity of EBV-CTL in this patient population Not all patients responded however suggesting the need for further improvement We propose that CTL failure can be overcome by increasing the specificity of the infused CTL product That is infusion of CTL specific for LMP1 and LMP2 will produce greater clinical benefit than EBV-specific CTL The rationale for this approach is straight forward EBV-specific CTL lines generated by standard methods are dominated by T-cell clones not reactive to the subdominant EBV proteins LMP1 and LMP2 expressed in NPC We also propose that the failure of adoptively transferred CTL to measurably expand in the peripheral blood of NPC patients is a consequence both of lymphoid homeostasis in these lympho-replete patients and of the inhibitory T-cell infiltrate at the sites of disease We will therefore use monoclonal antibodies targeting the CD45 antigen CD45 MAbs to lymphodeplete NPC patients prior to the infusion of EBV-specific CTL Preliminary results indicate that CD45 MAb depletion can augment CTL expansion and that such expansion is associated with a higher disease response rate We will confirm and extend these promising new data in this Phase I clinical trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20996-DELLA | OTHER | Baylor College of Medicine | None |