Ignite Creation Date:
2024-05-06 @ 12:28 PM
Last Modification Date:
2024-10-26 @ 12:59 PM
Study NCT ID:
NCT03769532
Status:
RECRUITING
Last Update Posted:
2022-11-15
First Post:
2018-12-05
Brief Title:
MRD-guided Treatment in NPM1mut AML Patients
Sponsor:
Technische Universität Dresden
Organization:
Technische Universität Dresden
Study Overview
Official Title:
MRD-guided Treatment With Pembrolizumab and Azacitidine in NPM1mut AML Patients With an Imminent Hematological Relapse
Status:
RECRUITING
Status Verified Date:
2022-11
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:
PEMAZA
Brief Summary:
Evaluation the safety and efficacy of Pembrolizumab PEM when administered in combination with standard Azacitidine AZA in nucleophosmin NPM1 mutated AML patients with molecular relapse defined by the presence of measurable residual disease MRD
Detailed Description:
Azacitidine is an effective and well established therapy in patients with acute myeloid leukemia AML In fact in previous measurable residual disease MRD triggered studies azacitidine allowed for a delay towards an overt hematological relapse in the majority of patients However the majority of patients ultimately relapsed even though they received multiple cycles of preemptive therapy Hypomethylating agents HMA can enhance antitumor immune responses by upregulating tumor antigene expression class 1 major histocompatibility complex and co-stimulatory molecules while concurrently dampening this antitumor effect by upregulating expression of checkpoint receptors or ligands including programmed cell death protein 1 PD-1 programmed cell death ligand 1 PD-L1 and cytotoxic T-lymphocyte-associated protein 4 CTLA-4 Upregulation of these immune checkpoint molecules might be a mechanism of resistance to hypomethylating drugs It has been shown that PD-L1 Messenger ribonucleic acid mRNA is up-regulated acute myeloid leukemia cluster of differentiation 34 CD34 cells and importantly patients resistant to treatment with hypomethylating agents such as azacitidine have an up-regulated expression compared to responding patients In addition it is known that PD-1 promoter demethylation correlates with a higher PD-1 expression and a worse response rate to hypomethylating agents as well as a shorter overall survival In this context it is of note that PD-1 promoter demethylation can be caused by hypomethylating agents and hence the mode of action of the drug itself could cause resistance to therapy in these patients This might also explain why hypomethylating agents are not curative and can not eradicate early leukemic progenitor cells The investigators therefore perform a phase II trial evaluating a combination therapy of pembrolizumab and azacitidine in nucleophosmin NPM1 mutated AML patients with MRD and impending hematological relapse after conventional chemotherapy This trial aims at improving response rates observed with single agent azacitidine within the studies NCT00422890 and NCT01462578
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None