Ignite Creation Date:
2024-05-06 @ 3:57 PM
Last Modification Date:
2024-10-26 @ 2:00 PM
Study NCT ID:
NCT04817241
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2021-03-25
Brief Title:
Testing Oral Decitabine and Cedazuridine ASTX727 in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Clinical Evaluation of ASTX727 in Combination With Venetoclax All-Oral Therapy vs Standard of Care Cytarabine and Anthracycline Induction Chemotherapy for Younger FLT3WT Patients With ELN High- Risk Acute Myeloid Leukemia
Status:
ACTIVE_NOT_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 IbII trial studies the effects of ASTX727 decitabine and cedazuridine in combination with venetoclax in treating patients with higher-risk acute myeloid leukemia patients who do not have a change in the gene called fms-like tyrosine kinase 3 FLT3 Decitabine is in a class of medications called hypomethylation agents It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow Cedazuridine is an enzyme inhibitor It helps to increase the amount of decitabine in the body so that the medication will have a greater effect Venetoclax is in a class of medications called B-cell lymphoma-2 BCL-2 inhibitors Venetoclax may stop the growth of cancer cells by blocking BCL-2 a protein needed for cancer cell survival Venetoclax and decitabine are commonly given together for older patients with AML ASTX727 a pill form of decitabine cedazuridine has been found to be equal to decitabine given intravenously and this part of the study is to confirm that venetoclax and ASTX727 is as safe as venetoclax and decitabine given intravenously This study allows for lowering doses of study drugs to assure the dose chosen for the randomized study second portion of this trial is safe and tolerable for people Giving ASTX727 in combination with venetoclax may help in the treatment of patients with higher-risk acute myeloid leukemia
Detailed Description:
PRIMARY OBJECTIVES
I To determine and compare the preliminary efficacy of venetoclax ASTX727 versus vs standard anthracycline induction therapy 73 with a primary endpoint of event-free survival EFS
SECONDARY OBJECTIVES
I To determine the complete response complete response CR complete response with incomplete bone marrow recovery CRi rate in patients with treatment naive FLT3 wild type WT acute myeloid leukemia AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
II To determine the duration of response DoR in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
III To determine the progression free survival PFS of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
IV To determine the overall response rate ORR in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
V To determine the overall survival OS of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
VI To determine the proportion of patients receiving stem cell transplantation SCT in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
VII To identify mutational burdens in venetoclax ASTX727 sensitive vs resistant AML leukemia initiating cells LICs
EXPLORATORY OBJECTIVES
I To identify transcriptomic signatures in venetoclax ASTX727 sensitive vs resistant AML LICs
II Determine the utility of high-throughput phenotype-based assessment of drug efficacy for predicting patient response to venetoclax ASTX727
III Determine if treatment failure is a function of therapy sequence or results in resistance to the alternative therapy by conducting a co-clinical trial via patient-derived xenograft PDX
IV To characterize the pharmacokinetics of venetoclax V To determine the morphologic leukemia-free state MLFS rate in patients with treatment naïve FLT3WT AML treated with venetoclax and ASTX727 vs 73 therapy
OUTLINE This is a phase Ib dose de-escalation study followed by a phase II randomized study
PHASE Ib Patients receive ASTX727 decitabine and cedazuridine orally PO once daily QD on days 1-4 or 1-5 of each cycle and venetoclax PO QD on days 1-28 or days 1-21 of each cycle Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial
PHASE II Patients are randomized to 1 of 2 arms
ARM I Patients receive ASTX727 PO QD at the recommended phase II dose and venetoclax PO QD on days 1-28 of each cycle Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial
ARM II Patients receive cytarabine intravenously IV over 24 hours on days 1-7 of each cycle and daunorubicin IV over 10-30 minutes on days 1-3 of each cycle Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy throughout the trial
After completion of study treatment patients are followed up every 3 months for up to 5 years
I To determine and compare the preliminary efficacy of venetoclax ASTX727 versus vs standard anthracycline induction therapy 73 with a primary endpoint of event-free survival EFS
SECONDARY OBJECTIVES
I To determine the complete response complete response CR complete response with incomplete bone marrow recovery CRi rate in patients with treatment naive FLT3 wild type WT acute myeloid leukemia AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
II To determine the duration of response DoR in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
III To determine the progression free survival PFS of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
IV To determine the overall response rate ORR in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
V To determine the overall survival OS of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
VI To determine the proportion of patients receiving stem cell transplantation SCT in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs standard anthracycline induction therapy 73
VII To identify mutational burdens in venetoclax ASTX727 sensitive vs resistant AML leukemia initiating cells LICs
EXPLORATORY OBJECTIVES
I To identify transcriptomic signatures in venetoclax ASTX727 sensitive vs resistant AML LICs
II Determine the utility of high-throughput phenotype-based assessment of drug efficacy for predicting patient response to venetoclax ASTX727
III Determine if treatment failure is a function of therapy sequence or results in resistance to the alternative therapy by conducting a co-clinical trial via patient-derived xenograft PDX
IV To characterize the pharmacokinetics of venetoclax V To determine the morphologic leukemia-free state MLFS rate in patients with treatment naïve FLT3WT AML treated with venetoclax and ASTX727 vs 73 therapy
OUTLINE This is a phase Ib dose de-escalation study followed by a phase II randomized study
PHASE Ib Patients receive ASTX727 decitabine and cedazuridine orally PO once daily QD on days 1-4 or 1-5 of each cycle and venetoclax PO QD on days 1-28 or days 1-21 of each cycle Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial
PHASE II Patients are randomized to 1 of 2 arms
ARM I Patients receive ASTX727 PO QD at the recommended phase II dose and venetoclax PO QD on days 1-28 of each cycle Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial
ARM II Patients receive cytarabine intravenously IV over 24 hours on days 1-7 of each cycle and daunorubicin IV over 10-30 minutes on days 1-3 of each cycle Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy throughout the trial
After completion of study treatment patients are followed up every 3 months for up to 5 years
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 |
|---|---|---|---|
| NCI-2021-02246 | REGISTRY | None | None |
| VICCNCIHEM10417 | None | None | None |
| 10417 | OTHER | None | None |
| 10417 | OTHER | None | None |
| UM1CA186689 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186689 |