Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06649227
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-15
Brief Title:
Study Investigating the Safety of CD19 CAR-T Cells in RelapsedRefractory AML Expressing CD19
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Prospective Non-randomized Phase I Study Investigating the Safety of CD19 CAR-T Cells in Patients With RefractoryRelapsed AML Expressing CD19
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CARLA-M19
Brief Summary:
RefractoryRelapsed RR acute myeloid leukemia AML is associated with a dis-mal prognosis
In some subsets of AML such as AML driven by the t821 translocation leading to the RUNX1-RUNX1T1 AML1-ETO fusion transcript expression CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 of cases Interestingly the expression of the CD19 antigen is also detected in the CD34 CD38-population leukemic stem cells
t821 AML subtype has a rather good prognosis with an intensive chemotherapy regimen but relapses occur in around 40 of the patients and new therapeutic options are needed for these patients
Plesa et al reported a successful treatment of a refractory t821 AML with bispecific monoclonal antibodies that targets CD19 More recently Danylesko et al have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t821 AML1 The same group has just submitted an abstract of 6 treated patients to the European Haematology Association EHA 2023 meet-ing Six patients adults-5 child-1 with t8 21 AML confirmed by cytogenetic and FISH and aberrant CD19 expression were included One patient had a complex karyotype Molecular analysis for CKIT NPM1 IDH1 IDH2 and CBPa were nega-tive in all pts One pt harbors the FLT3 ITD and TKD mutations Median number of previous chemotherapy CT lines was 4 3-8 Four patients were with chemo re-sistant relapse post allo-HCT MSD-1 1010 MUD -3 5-18 months before CAR T-cell infusion All patients developed CRS grade 1-3 and were treated with iv tocili-zumab and dexamethasone 26 patients suffered from ICANS and were treated with steroids In 46 patients day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t821 by FISH confirming clinical and cyto-genetic remission while 26 pts with progressive AML had no response Danylesko etal Abstract EHA 2023 submitted
Interestingly other subsets of AML display an aberrant expression of CD19 These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with RR AML expressing this antigen
In this study we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsedrefractory AML expressing CD19 for whom no curative alternatives are available
To this end CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy Miltenyi Biotec in academic setting
In some subsets of AML such as AML driven by the t821 translocation leading to the RUNX1-RUNX1T1 AML1-ETO fusion transcript expression CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 of cases Interestingly the expression of the CD19 antigen is also detected in the CD34 CD38-population leukemic stem cells
t821 AML subtype has a rather good prognosis with an intensive chemotherapy regimen but relapses occur in around 40 of the patients and new therapeutic options are needed for these patients
Plesa et al reported a successful treatment of a refractory t821 AML with bispecific monoclonal antibodies that targets CD19 More recently Danylesko et al have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t821 AML1 The same group has just submitted an abstract of 6 treated patients to the European Haematology Association EHA 2023 meet-ing Six patients adults-5 child-1 with t8 21 AML confirmed by cytogenetic and FISH and aberrant CD19 expression were included One patient had a complex karyotype Molecular analysis for CKIT NPM1 IDH1 IDH2 and CBPa were nega-tive in all pts One pt harbors the FLT3 ITD and TKD mutations Median number of previous chemotherapy CT lines was 4 3-8 Four patients were with chemo re-sistant relapse post allo-HCT MSD-1 1010 MUD -3 5-18 months before CAR T-cell infusion All patients developed CRS grade 1-3 and were treated with iv tocili-zumab and dexamethasone 26 patients suffered from ICANS and were treated with steroids In 46 patients day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t821 by FISH confirming clinical and cyto-genetic remission while 26 pts with progressive AML had no response Danylesko etal Abstract EHA 2023 submitted
Interestingly other subsets of AML display an aberrant expression of CD19 These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with RR AML expressing this antigen
In this study we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsedrefractory AML expressing CD19 for whom no curative alternatives are available
To this end CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy Miltenyi Biotec in academic setting
Detailed Description:
None
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