Ignite Creation Date:
2024-07-17 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06484062
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-06-29
Brief Title:
Testing the Anti-cancer Drug Cirtuvivint and Its Combination With ASTX727 and ASTX727 With Venetoclax to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study Evaluating the Safety of Cirtuvivint as Monotherapy and in Combination With ASTX727 and ASTX727 Venetoclax in Patients With Myelodysplastic Syndromes MDS and Acute Myeloid Leukemia 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:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects and best dose of SM08502 cirtuvivint alone and in combination with ASTX727 as well as ASTX727 and venetoclax in treating patients with acute myeloid leukemia AML and myelodysplastic syndromes MDS Cirtuvivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth ASTX727 is a combination of two drugs decitabine and cedazuridine 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 in a class of medications called cytidine deaminase inhibitors It prevents the breakdown of decitabine making it more available in the body so that decitabine will have a greater effect 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 cirtuvivint alone or in combination with ASTX727 or ASTX727 and venetoclax may be safe tolerable andor effective in treating patients with AML and MDS
Detailed Description:
PRIMARY OBJECTIVE
I To determine the recommended phase 2 dose RP2D of SM08502 cirtuvivint as monotherapy in RelapsedRefractory RR acute myeloid leukemia AML and myelodysplastic syndromes MDS Cohort I and II and in combination with decitabine and cedazuridine ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
SECONDARY OBJECTIVES
I To assess the safetytolerability of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
II To assess the pharmacokinetics PK and pharmacodynamics PD of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
III To determine the preliminary efficacy of the combination of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV by assessing the response rate as defined by the 2022 European LeukemiaNet ELN response criteria for AML Döhner et al 2022 and International Working Group IWG 2023 response criteria for MDS Zeidan et al 2023
IV To explore survival outcomes achieved with SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV by assessing 1 year event free survival EFS and overall survival OS rate
V To observe and record anti-tumor activity VI To evaluate the best schedule to move forward with in Phase 2
OUTLINE This is a dose-escalation study of cirtuvivint as monotherapy followed by an expansion study in combination with ASTX727 and ASTX727 plus venetoclax Patients are assigned to 1 of 4 cohorts
COHORT I Patients receive cirtuvivint orally PO once daily QD Monday-Friday on days 1-5 8-12 15-19 and 22-26 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO or multigated acquisition scan MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT II Patients receive cirtuvivint PO once QD on days 1 4 8 11 15 18 22 and 25 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT III Patients receive cirtuvivint PO QD on days 1 4 8 11 15 18 22 and 25 and ASTX727 PO QD on days 1-5 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT IV Patients receive cirtuvivint PO QD on days 1 4 8 11 15 18 22 and 25 ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
After completion of study treatment patients are followed up for 30 days every 3 months for 2 years then every 6 months for up to 3 years
I To determine the recommended phase 2 dose RP2D of SM08502 cirtuvivint as monotherapy in RelapsedRefractory RR acute myeloid leukemia AML and myelodysplastic syndromes MDS Cohort I and II and in combination with decitabine and cedazuridine ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
SECONDARY OBJECTIVES
I To assess the safetytolerability of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
II To assess the pharmacokinetics PK and pharmacodynamics PD of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV
III To determine the preliminary efficacy of the combination of SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV by assessing the response rate as defined by the 2022 European LeukemiaNet ELN response criteria for AML Döhner et al 2022 and International Working Group IWG 2023 response criteria for MDS Zeidan et al 2023
IV To explore survival outcomes achieved with SM08502 cirtuvivint as monotherapy in RR AML and MDS Cohort I and II and in combination with ASTX727 in frontline MDS Cohort III and in combination with ASTX727 venetoclax in frontline AML Cohort IV by assessing 1 year event free survival EFS and overall survival OS rate
V To observe and record anti-tumor activity VI To evaluate the best schedule to move forward with in Phase 2
OUTLINE This is a dose-escalation study of cirtuvivint as monotherapy followed by an expansion study in combination with ASTX727 and ASTX727 plus venetoclax Patients are assigned to 1 of 4 cohorts
COHORT I Patients receive cirtuvivint orally PO once daily QD Monday-Friday on days 1-5 8-12 15-19 and 22-26 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO or multigated acquisition scan MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT II Patients receive cirtuvivint PO once QD on days 1 4 8 11 15 18 22 and 25 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT III Patients receive cirtuvivint PO QD on days 1 4 8 11 15 18 22 and 25 and ASTX727 PO QD on days 1-5 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
COHORT IV Patients receive cirtuvivint PO QD on days 1 4 8 11 15 18 22 and 25 ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-28 of each cycle Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo ECHO or MUGA at screening In addition patients undergo blood sample collection and bone marrow aspiration and biopsy at screening and on study
After completion of study treatment patients are followed up for 30 days every 3 months for 2 years then every 6 months for up to 3 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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-05326 | REGISTRY | None | None |
| 10674 | OTHER | None | None |
| 10674 | OTHER | None | None |
| UM1CA186709 | NIH | None | None |