Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06366789
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-04-05
Brief Title:
Dose Escalation and Expansion Study to Evaluate the Safety PK PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia
Sponsor:
Eilean Therapeutics
Organization:
Eilean Therapeutics
Study Overview
Official Title:
A Phase 1 Open-label Dose Escalation and Dose Expansion Multicenter Clinical Trial to Evaluate the Safety Pharmacokinetics Pharmacodynamics and Preliminary Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia AML
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
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:
None
Brief Summary:
This is a clinical study aiming to assess pharmacokinetics pharmacodynamics and preliminary efficacy of ZE46-0134 in patients with FLT3 mutated Relapsed or Refractory Acute Myeloid Leukemia
Detailed Description:
This is a Phase 1 open-label multicenter dose escalation and dose optimization study to evaluate the safety tolerability PK PD and preliminary efficacy of ZE46-0134 in adult patients with relapsed or refractory AML with FLT3-ITD andor FLT3-TKD mutations Patients with AML that are out-patients or hospitalized due to their AML can be enrolled in the study
The study will be run in 2 parts Part 1 will be dose escalation and determination of MTD and Part 2 will be dose expansion
In Part 1 of the study 3 to 6 eligible patients will be sequentially enrolled into each of 5 planned dose level cohorts Patients will receive up to 24 cycles 28 days each of study treatment For patients that continued to derive benefit after 24 cycles of treatment continuation of ZE46-0134 therapy will be considered
In Part 2 the dose expansion phase will involve enrolling up to 30 patients across 2 dose cohorts ie 15 patients per cohort ZE46-0134 will be dosed as described for Part 1 of the study The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study
Indication background information
Acute myeloid leukemia AML comprises a heterogeneous group of aggressive blood cell cancers that arise from clonal expansion of malignant hematopoietic precursor cells in the bone marrow BM and is the most commonly diagnosed adult leukemia with a median age at diagnosis is 68 years with an overall survival OS rate of 298 As patients age there is a 10 decrease in 5-year OS for every additional decade of life with a 5-year OS of 04 in patients age 85 years1 Furthermore remission rates and OS depend on a number of other factors including cytogenetics previous BM disorders and comorbidities
FMS-like tyrosine kinase-3 FLT3 is a receptor tyrosine kinase RTK primarily expressed on immature hematopoietic progenitors and hematopoietic stem cells FLT3 signaling is initiated when FLT3 ligand binds to FLT3 inducing the dimerization and activation of FLT3 via autophosphorylation This then activates downstream signaling of phosphoinositide 3-kinaseprotein kinase B PI3KPKB mitogen-activated protein kinase MAPK and JAK2STAT5 which leads to cell proliferation and suppression of apoptosis2
FLT3 kinase is directly implicated in the pathogenesis of hematologic malignancies particularly AML FLT3 mutations are the most frequently identified mutations in AML patients Activating mutations in FLT3 which are FLT3-internal tandom duplication ITD and FLT3 tyrosine kinase domain TKD mutations account for 30 of all AML cases2 As a result of these mutations the FLT3 receptor is continuously activated leading to the continuous activation of downstream signaling pathways PI3KAKT MAPK and signal transducer and activator of transcription STAT5 resulting in increased cell proliferation and decreased apoptosis
The study will be run in 2 parts Part 1 will be dose escalation and determination of MTD and Part 2 will be dose expansion
In Part 1 of the study 3 to 6 eligible patients will be sequentially enrolled into each of 5 planned dose level cohorts Patients will receive up to 24 cycles 28 days each of study treatment For patients that continued to derive benefit after 24 cycles of treatment continuation of ZE46-0134 therapy will be considered
In Part 2 the dose expansion phase will involve enrolling up to 30 patients across 2 dose cohorts ie 15 patients per cohort ZE46-0134 will be dosed as described for Part 1 of the study The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study
Indication background information
Acute myeloid leukemia AML comprises a heterogeneous group of aggressive blood cell cancers that arise from clonal expansion of malignant hematopoietic precursor cells in the bone marrow BM and is the most commonly diagnosed adult leukemia with a median age at diagnosis is 68 years with an overall survival OS rate of 298 As patients age there is a 10 decrease in 5-year OS for every additional decade of life with a 5-year OS of 04 in patients age 85 years1 Furthermore remission rates and OS depend on a number of other factors including cytogenetics previous BM disorders and comorbidities
FMS-like tyrosine kinase-3 FLT3 is a receptor tyrosine kinase RTK primarily expressed on immature hematopoietic progenitors and hematopoietic stem cells FLT3 signaling is initiated when FLT3 ligand binds to FLT3 inducing the dimerization and activation of FLT3 via autophosphorylation This then activates downstream signaling of phosphoinositide 3-kinaseprotein kinase B PI3KPKB mitogen-activated protein kinase MAPK and JAK2STAT5 which leads to cell proliferation and suppression of apoptosis2
FLT3 kinase is directly implicated in the pathogenesis of hematologic malignancies particularly AML FLT3 mutations are the most frequently identified mutations in AML patients Activating mutations in FLT3 which are FLT3-internal tandom duplication ITD and FLT3 tyrosine kinase domain TKD mutations account for 30 of all AML cases2 As a result of these mutations the FLT3 receptor is continuously activated leading to the continuous activation of downstream signaling pathways PI3KAKT MAPK and signal transducer and activator of transcription STAT5 resulting in increased cell proliferation and decreased apoptosis
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CT-2024-CTN-00161-1 | OTHER | Therapeutic Goods Administration | None |