Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06454409
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-12
First Post:
2024-06-06
Brief Title:
Regorafenib in Combination With Venetoclax and Azacitidine for the Treatment of Patients With Relapsed or Refractory Acute Myeloid Leukemia
Sponsor:
City of Hope Medical Center
Organization:
City of Hope Medical Center
Study Overview
Official Title:
A Phase 1b Study of the Multi-Kinase Inhibitor Regorafenib in Combination With the BCL-2 Inhibitor Venetoclax Plus Azacitidine in Patients With RelapsedRefractory Acute Myeloid Leukemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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 phase Ib trial tests the safety side effects best dose and effectiveness of regorafenib in combination with venetoclax and azacitidine in treating patients with acute myeloid leukemia AML that has come back after a period of improvement relapsed or that has not responded to previous treatment refractory Regorafenib is in a class of medications called kinase inhibitors It works by blocking the action of an abnormal protein that signals cancer cells to multiply This helps to slow or stop the spread of cancer cells 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 Azacitidine is in a class of medications called demethylation agents It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells Giving regorafenib in combination with venetoclax and azacitidine may be safe tolerable andor effective in treating patients with relapsed or refractory AML
Detailed Description:
PRIMARY OBJECTIVES
I Evaluate the safety and tolerability of the multikinase inhibitor regorafenib in combination with the BCL2 inhibitorBH3-mimetic venetoclax plus the hypomethylating agent azacitidine in patients with relapsedrefractory RR acute myeloid leukemia AML
II Determine the maximum tolerated dose MTD and recommended phase 2 dose RP2D of regorafenib when co- administered with venetoclax and azacitidine
SECONDARY OBJECTIVES
I Evaluate the anti-leukemic activity as assessed by overall response rate ORR complete remission CR CR with incomplete hematologic recovery CRi CR with partial hematologic recovery CRh partial remission PR within the first 28 days cycle 1
II Evaluate the anti-leukemic activity as assessed by complete remission CRCRiCRh overall response ORR CRCRiCRhPR and minimal residual disease MRD- rate and duration over the study period
III Estimate overall survival OS progression-free survival PFS and duration of response DOR rate at 6 months and 1 year
EXPLORATORY OBJECTIVES
I Determine biomarkers that may be predictive of regorafenib activity in this combination
II To evaluate expression levels of VEGF phosphatidylinositol-glycan PIG and soluble sVEGFR2 pre and post-treatment
III To evaluate changes in angiogenesis and inflammation pre and post treatment by gene expression
IV To characterize gene expression changes including genes involved in the RASMAPK pathway by ribonucleic acid RNA sequencing pre and post treatment with regorafenib when co-administered with venetoclax and azacitidine
V To evaluate changes in the gene mutation status of leukemic cells before and after treatment with regorafenib azacitidine and venetoclax
VI Evaluate changes to phosphorylated phospho-ERK after treatment with combination therapy
OUTLINE This is a dose-escalation study of regorafenib in combination with venetoclax and azacitidine followed by a dose-expansion study
Patients receive regorafenib orally PO once daily QD on days 1-21 of each cycle venetoclax PO QD on days 1-21 of each cycle and azacitidine intravenously IV over 10-40 minutes on days 1-7 of each cycle Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration during screening and on study as well as blood sample collection on study
After completion of study treatment patients are followed up at 30 days then every 3 months for up to 1 year
I Evaluate the safety and tolerability of the multikinase inhibitor regorafenib in combination with the BCL2 inhibitorBH3-mimetic venetoclax plus the hypomethylating agent azacitidine in patients with relapsedrefractory RR acute myeloid leukemia AML
II Determine the maximum tolerated dose MTD and recommended phase 2 dose RP2D of regorafenib when co- administered with venetoclax and azacitidine
SECONDARY OBJECTIVES
I Evaluate the anti-leukemic activity as assessed by overall response rate ORR complete remission CR CR with incomplete hematologic recovery CRi CR with partial hematologic recovery CRh partial remission PR within the first 28 days cycle 1
II Evaluate the anti-leukemic activity as assessed by complete remission CRCRiCRh overall response ORR CRCRiCRhPR and minimal residual disease MRD- rate and duration over the study period
III Estimate overall survival OS progression-free survival PFS and duration of response DOR rate at 6 months and 1 year
EXPLORATORY OBJECTIVES
I Determine biomarkers that may be predictive of regorafenib activity in this combination
II To evaluate expression levels of VEGF phosphatidylinositol-glycan PIG and soluble sVEGFR2 pre and post-treatment
III To evaluate changes in angiogenesis and inflammation pre and post treatment by gene expression
IV To characterize gene expression changes including genes involved in the RASMAPK pathway by ribonucleic acid RNA sequencing pre and post treatment with regorafenib when co-administered with venetoclax and azacitidine
V To evaluate changes in the gene mutation status of leukemic cells before and after treatment with regorafenib azacitidine and venetoclax
VI Evaluate changes to phosphorylated phospho-ERK after treatment with combination therapy
OUTLINE This is a dose-escalation study of regorafenib in combination with venetoclax and azacitidine followed by a dose-expansion study
Patients receive regorafenib orally PO once daily QD on days 1-21 of each cycle venetoclax PO QD on days 1-21 of each cycle and azacitidine intravenously IV over 10-40 minutes on days 1-7 of each cycle Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration during screening and on study as well as blood sample collection on study
After completion of study treatment patients are followed up at 30 days then every 3 months for up to 1 year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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 |
|---|---|---|---|
| P30CA033572 | NIH | City of Hope Medical Center | httpsreporternihgovquickSearchP30CA033572 |
| NCI-2024-04611 | REGISTRY | None | None |
| 23713 | OTHER | None | None |