Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06514261
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-20
Brief Title:
Testing the Combination of an Anti-Cancer Drug Iadademstat With Other Anti-Cancer Drugs Venetoclax and Azacitidine for Treating AML
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML
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:
None
Brief Summary:
This phase I trial tests safety side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia AML who have not receive treatment treatment naive Chemotherapy drugs such as iadademstat and azacitidine work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Venetoclax is in a class of medications called B-cell lymphoma-2 BCL-2 inhibitors It may stop the growth of cancer cells by blocking Bcl-2 a protein needed for cancer cell survival Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML
Detailed Description:
PRIMARY OBJECTIVE
I To determine the recommended phase 2 dose RP2D and safety profile of iadademstat in combination with venetoclax and azacitidine
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity including evaluating the overall response rate ORR defined as complete remission CR CR with incomplete hematologic recovery Cri or CR with partial hematologic recovery CRh
II To evaluate the measurable residual disease MRD-negative composite CR cCR rate after 1 2 and 3 cycles using multiparameter flow cytometry MFC and evaluate event-free survival EFS overall survival OS and duration of response DoR
III To determine if treatment will be associated with expansion of high risk molecular PTPN11 NRAS KRAS NF1 and TP53 and cytogenetic complex karyotype markers over time
EXPLORATORY OBJECTIVES
I To determine the rate of MRD-negative cCR across molecular PTPN11 NRAS KRAS NF1 and TP53 and cytogenetic complex karyotype subgroups
II To document the effect of therapy on LSD1-target engagement
III To determine if secondary resistance remission with therapy then relapse in both arms is associated with
IIIa Acquisition of resistance mutations including BCL-2 and BAX IIIb Development or expansion of mutations that activate RASMAPKFLT3 including NRAS KRAS PTPN11 NF1 and FLT3-ITD
IIIc Over-expression of resistance proteins such as MCL-1 or BCL-XL IV To determine pharmacokinetics PK in the triplet therapy of iadademstat azacitidine and venetoclax
V To explore PKphasrmacodynamic PD relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat azacitidine and venetoclax
VI To evaluate the association between time to achieve an MRD-negative cCR and EFS OS
OUTLINE This is a dose-escalation study of iadademstat and venetocalx in combination with azacitidine
INDUCTION Patients receive iadademstat orally PO once per day QD on days 1-5 8-12 and may also receive it on days 15-19 venetoclax PO QD on days 1-14 or 1-21 and azacitidine intravenously IV over 10-40 minutes or subcutaneously SC on days 1-7 or 1-5 and 8-9 of each cycle Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive iadademstat PO QD on days 1-5 8-12 and may also receive it on days 15-19 venetoclax PO QD on days 1-7 or 1-14 and azacitidine IV over 10-40 minutes or SC on days 1-7 or 1-5 and 8-9 of each cycle Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study
After completion of study treatment patients are followed every 3-4 months for up to 2 years
I To determine the recommended phase 2 dose RP2D and safety profile of iadademstat in combination with venetoclax and azacitidine
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity including evaluating the overall response rate ORR defined as complete remission CR CR with incomplete hematologic recovery Cri or CR with partial hematologic recovery CRh
II To evaluate the measurable residual disease MRD-negative composite CR cCR rate after 1 2 and 3 cycles using multiparameter flow cytometry MFC and evaluate event-free survival EFS overall survival OS and duration of response DoR
III To determine if treatment will be associated with expansion of high risk molecular PTPN11 NRAS KRAS NF1 and TP53 and cytogenetic complex karyotype markers over time
EXPLORATORY OBJECTIVES
I To determine the rate of MRD-negative cCR across molecular PTPN11 NRAS KRAS NF1 and TP53 and cytogenetic complex karyotype subgroups
II To document the effect of therapy on LSD1-target engagement
III To determine if secondary resistance remission with therapy then relapse in both arms is associated with
IIIa Acquisition of resistance mutations including BCL-2 and BAX IIIb Development or expansion of mutations that activate RASMAPKFLT3 including NRAS KRAS PTPN11 NF1 and FLT3-ITD
IIIc Over-expression of resistance proteins such as MCL-1 or BCL-XL IV To determine pharmacokinetics PK in the triplet therapy of iadademstat azacitidine and venetoclax
V To explore PKphasrmacodynamic PD relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat azacitidine and venetoclax
VI To evaluate the association between time to achieve an MRD-negative cCR and EFS OS
OUTLINE This is a dose-escalation study of iadademstat and venetocalx in combination with azacitidine
INDUCTION Patients receive iadademstat orally PO once per day QD on days 1-5 8-12 and may also receive it on days 15-19 venetoclax PO QD on days 1-14 or 1-21 and azacitidine intravenously IV over 10-40 minutes or subcutaneously SC on days 1-7 or 1-5 and 8-9 of each cycle Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION Patients receive iadademstat PO QD on days 1-5 8-12 and may also receive it on days 15-19 venetoclax PO QD on days 1-7 or 1-14 and azacitidine IV over 10-40 minutes or SC on days 1-7 or 1-5 and 8-9 of each cycle Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study
After completion of study treatment patients are followed every 3-4 months for up to 2 years
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