Ignite Creation Date:
2024-05-06 @ 2:02 PM
Last Modification Date:
2024-10-26 @ 1:23 PM
Study NCT ID:
NCT04190550
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-04
First Post:
2019-12-06
Brief Title:
Testing the Addition of an Anti-cancer Drug Navtemadlin to the Usual Treatments Cytarabine and Idarubicin in Patients With Acute Myeloid Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1b Study With Expansion Cohort of Escalating Doses of KRT-232 AMG 232 Administered in Combination With Standard Induction Chemotherapy Cytarabine and Idarubicin in Newly Diagnosed Acute Myelogenous Leukemia AML
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
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 studies the side effects and best dose of navtemadlin when given together with the standard chemotherapy drugs cytarabine and idarubicin in patients with acute myeloid leukemia Navtemadlin may stop the growth of cancer cells by blocking a protein called MDM2 that is needed for cell growth Chemotherapy drugs such as cytarabine and idarubicin 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 Giving navtemadlin with cytarabine and idarubicin may stabilize cancer for longer when compared to giving usual treatments alone
Detailed Description:
PRIMARY OBJECTIVE
I To evaluate the toxicities of navtemadlin KRT-232 AMG 232 cytarabine and idarubicin hydrochloride idarubicin and to determine the maximum tolerated dose MTDrecommended phase 2 dose RP2D of KRT-232 AMG 232 cytarabine and idarubicin
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To evaluate the pharmacokinetic PK profiles of KRT-232 AMG 232 cytarabine and idarubicin when used in combination
III To evaluate p53 signaling induced by KRT-232 AMG 232 cytarabine and idarubicin
IV To correlate KRT-232 AMG 232 cytarabine and idarubicin exposure with pharmacodynamics endpoints efficacy toxicity changes in p53 signaling
EXPLORATORY OBJECTIVES
I To evaluate the response rate RR and progression free survival PFS of KRT-232 AMG 232 cytarabine and idarubicin in acute myeloid leukemia AML
II To evaluate potential predictive biomarkers including MTF2 and H3K27me3 of response to KRT-232 AMG 232 cytarabine and idarubicin in AML
III To evaluate the pharmacodynamic PD effects of KRT-232 and induction chemotherapy in AML blasts
OUTLINE This is a dose-escalation study of navtemadlin
Patients receive navtemadlin orally PO once daily QD on days 1-7 cytarabine intravenously IV twice daily BID over 3 hours on days 1-7 and idarubicin IV over 10-15 minutes on days 1-3 Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients with residual disease may receive cytarabine IV BID over 3 hours for 5 days and idarubicin IV over 10-15 minutes for 2 days starting between days 14-21 of cycle 1 or the second cycle of navtemadlin cytarabine and idarubicin Patients who achieve a complete response CR or a CR with incomplete hematologic recovery CRi in either cycle 1 or 2 may receive cytarabine IV BID over 3 hours on days 1 3 and 5 for 3-4 additional 28 to 35-day cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 3 months for 2 years then every 6 months thereafter
I To evaluate the toxicities of navtemadlin KRT-232 AMG 232 cytarabine and idarubicin hydrochloride idarubicin and to determine the maximum tolerated dose MTDrecommended phase 2 dose RP2D of KRT-232 AMG 232 cytarabine and idarubicin
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity II To evaluate the pharmacokinetic PK profiles of KRT-232 AMG 232 cytarabine and idarubicin when used in combination
III To evaluate p53 signaling induced by KRT-232 AMG 232 cytarabine and idarubicin
IV To correlate KRT-232 AMG 232 cytarabine and idarubicin exposure with pharmacodynamics endpoints efficacy toxicity changes in p53 signaling
EXPLORATORY OBJECTIVES
I To evaluate the response rate RR and progression free survival PFS of KRT-232 AMG 232 cytarabine and idarubicin in acute myeloid leukemia AML
II To evaluate potential predictive biomarkers including MTF2 and H3K27me3 of response to KRT-232 AMG 232 cytarabine and idarubicin in AML
III To evaluate the pharmacodynamic PD effects of KRT-232 and induction chemotherapy in AML blasts
OUTLINE This is a dose-escalation study of navtemadlin
Patients receive navtemadlin orally PO once daily QD on days 1-7 cytarabine intravenously IV twice daily BID over 3 hours on days 1-7 and idarubicin IV over 10-15 minutes on days 1-3 Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients with residual disease may receive cytarabine IV BID over 3 hours for 5 days and idarubicin IV over 10-15 minutes for 2 days starting between days 14-21 of cycle 1 or the second cycle of navtemadlin cytarabine and idarubicin Patients who achieve a complete response CR or a CR with incomplete hematologic recovery CRi in either cycle 1 or 2 may receive cytarabine IV BID over 3 hours on days 1 3 and 5 for 3-4 additional 28 to 35-day cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 3 months for 2 years then every 6 months thereafter
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 |
|---|---|---|---|
| UM1CA186717 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186717 |
| NCI-2019-08137 | REGISTRY | None | None |
| PHI-115 | None | None | None |
| 10367 | OTHER | None | None |
| 10367 | OTHER | None | None |