Ignite Creation Date:
2024-05-06 @ 2:07 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01976585
Status:
COMPLETED
Last Update Posted:
2022-09-22
First Post:
2013-10-30
Brief Title:
In Situ Vaccine for Low-Grade Lymphoma Combination of Intratumoral Flt3L and Poly-ICLC With Low-Dose Radiotherapy
Sponsor:
Joshua Brody
Organization:
Icahn School of Medicine at Mount Sinai
Study Overview
Official Title:
A Phase III Study of Intratumoral Injection of rhuFlt3LCDX-301 and Poly-ICLC in Combination With Low-Dose Radiotherapy in Low-Grade B-cell Lymphomas
Status:
COMPLETED
Status Verified Date:
2022-09
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:
None
Brief Summary:
Our recent trials combining local radiotherapy with intratumoral administration of TLR agonists - referred to as in situ vaccination - for patients with low-grade lymphoma demonstrated safety induction of anti-tumor CD8 T cell responses and partial and complete remissions of patients non-irradiated sites of disease with complete remissions lasting from months to more than three years
This iteration of the in situ vaccine approach builds on our prior work in ways that should improve its efficacy by adding Flt3L and changing the toll-like receptors TLR agonist to poly-ICLC -an optimal TLR agonist for the type of dendritic cells DC recruited by Flt3L The vaccine is thus in 3 phases
1 intratumoral Flt3L administration recruits DC to the tumor
2 low-dose radiotherapy to release tumor antigens
3 intratumoral poly-ICLC administration activates tumor-antigen loaded DC
This iteration of the in situ vaccine approach builds on our prior work in ways that should improve its efficacy by adding Flt3L and changing the toll-like receptors TLR agonist to poly-ICLC -an optimal TLR agonist for the type of dendritic cells DC recruited by Flt3L The vaccine is thus in 3 phases
1 intratumoral Flt3L administration recruits DC to the tumor
2 low-dose radiotherapy to release tumor antigens
3 intratumoral poly-ICLC administration activates tumor-antigen loaded DC
Detailed Description:
Lymphomas comprise the 5th most common cancer in the US with approximately 80000 new cases diagnosed in the US each year Low-grade B-cell lymphomas are the most prevalent subtype amongst these and are considered incurable with standard therapies Chemotherapy and monoclonal antibody therapy induce temporary remissions though disease generally recurs becomes progressively more resistant to therapy and ultimately therapy-resistant Standard therapies prolong survival though there is no standard of care regarding when to initiate therapy versus observation or the optimal sequence of different therapies Novel therapies are needed with distinct mechanisms and with greater tolerability profiles Immunotherapy has a long precedent of being able to cure low-grade lymphomas with allogeneic transplant being curative in a proportion of chemo-refractory patients though the morbidity of this procedure reduces its broader utilization
Previously we completed four trials combining local radiotherapy a standard of care for these diseases with intratumoral administration of TLR agonists - an approach we refer to as in situ vaccination for patients with previously untreated or relapsedrefractory low-grade lymphoma We demonstrated safety induction of anti-tumor CD8 T cell responses and partial and complete remissions of patients non-irradiated sites of disease1 2 The most recent trials compared previously untreated versus relapsedrefractory patients receiving the same therapy and observed superior responses in the former group presumably due to immunosuppressive effects of prior treatments in the latter group The in situ vaccine is premised on pre-clinical data showing this approach to be superior to systemic TLR agonist delivery3 and our clinical results reproduce this finding in situ vaccination yields superior response rates as compared to trials of systemic TLR agonist therapy for lymphoma4
This iteration of the in situ vaccine approach builds on our prior work in ways that should improve its efficacy by making two changes to the prior approach
1 intratumoral administration of rhuFlt3LCDX-301 to recruit dendritic cells to the tumor site
2 intratumoral administration of poly-ICLC Flt3L has been safely administered to patients with lymphoma5 and -pre-clinically- has been shown to induce tumor leukocyte infiltration and regression of lymphoma tumors6 7 A total of 36 healthy volunteers and 294 cancer patients were treated including only industry-sponsored studies with the prior formulation of this agent AMG 949 with excellent tolerability and 30 healthy volunteers were recently treated with the current formulation CDX-301 again with excellent tolerability
Poly-ICLC has been safely administered to patients with lymphoma8 and -pre-clinically- has been shown to induce natural killer NK cell cytolytic activity and regression of lymphoma tumors9-11 Over 600 healthy volunteers and cancer patients in 17 trials have been treated with comparable doses of poly-ICLC as that used here with excellent tolerability
Previously we completed four trials combining local radiotherapy a standard of care for these diseases with intratumoral administration of TLR agonists - an approach we refer to as in situ vaccination for patients with previously untreated or relapsedrefractory low-grade lymphoma We demonstrated safety induction of anti-tumor CD8 T cell responses and partial and complete remissions of patients non-irradiated sites of disease1 2 The most recent trials compared previously untreated versus relapsedrefractory patients receiving the same therapy and observed superior responses in the former group presumably due to immunosuppressive effects of prior treatments in the latter group The in situ vaccine is premised on pre-clinical data showing this approach to be superior to systemic TLR agonist delivery3 and our clinical results reproduce this finding in situ vaccination yields superior response rates as compared to trials of systemic TLR agonist therapy for lymphoma4
This iteration of the in situ vaccine approach builds on our prior work in ways that should improve its efficacy by making two changes to the prior approach
1 intratumoral administration of rhuFlt3LCDX-301 to recruit dendritic cells to the tumor site
2 intratumoral administration of poly-ICLC Flt3L has been safely administered to patients with lymphoma5 and -pre-clinically- has been shown to induce tumor leukocyte infiltration and regression of lymphoma tumors6 7 A total of 36 healthy volunteers and 294 cancer patients were treated including only industry-sponsored studies with the prior formulation of this agent AMG 949 with excellent tolerability and 30 healthy volunteers were recently treated with the current formulation CDX-301 again with excellent tolerability
Poly-ICLC has been safely administered to patients with lymphoma8 and -pre-clinically- has been shown to induce natural killer NK cell cytolytic activity and regression of lymphoma tumors9-11 Over 600 healthy volunteers and cancer patients in 17 trials have been treated with comparable doses of poly-ICLC as that used here with excellent tolerability
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