Ignite Creation Date:
2024-05-06 @ 7:04 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05886049
Status:
RECRUITING
Last Update Posted:
2024-06-25
First Post:
2023-06-01
Brief Title:
Testing the Addition of an Anti-cancer Drug SNDX-5613 to the Standard Chemotherapy Treatment Daunorubicin and Cytarabine for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLLKMT2A Gene
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1b Study of Menin Inhibitor SNDX-5613 in Combination With Daunorubicin and Cytarabine in Newly Diagnosed Patients With Acute Myeloid Leukemia and NPM1 MutatedFLT3 Wildtype or MLLKMT2A Rearranged Disease
Status:
RECRUITING
Status Verified Date:
2024-06
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 Ib trial tests the safety side effects and best dose of SNDX-5613 when given in combination with the standard chemotherapy treatment daunorubicin and cytarabine in treating patients with newly diagnosed acute myeloid leukemia that has changes in the NPM1 gene or MLLKMT2A gene SNDX-5613 blocks signals passed from one molecule to another inside cancer cells that are needed for cancer cell survival Drugs used in chemotherapy such as daunorubicin and cytarabine 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 Adding SNDX-5613 to the standard chemotherapy treatment may be able to shrink or stabilize the cancer for longer than the standard chemotherapy treatment alone
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD recommended phase 2 dose RP2D and safety of revumenib SNDX-5613 combined with 7 3 induction in newly diagnosed untreated NPM1-mutatedFLT3-ITD wild type and NPM1-mutatedFLT3-TKD wild type or MLLKMT2A-rearranged acute myeloid leukemia AML patients 18-75 years old who are candidates for intensive induction therapy
II To determine the maximum tolerated dose MTD recommended phase 2 dose RP2D and safety of SNDX-5613 combined with one cycle of consolidation with high dose cytarabine in newly diagnosed AML patients in complete responsecomplete response with incomplete count recovery CRCri after intensive induction therapy with 73 for NPM1-mutatedFLT3-ITD wild type and NPM1-mutatedFLT3-TKD wild type or MLL KMT2A-rearranged AML patients 18-75 years old who are candidates for intensive therapy
SECONDARY OBJECTIVES
I Evaluate the pharmacokinetics of SNDX-5613 with this combination regimen and characterize clinically relevant drug-drug interactions with antifungal agents
II To determine the number of patients with CRCRi out of the total number of patients treated at each dose level of this regimen
EXPLORATORY OBJECTIVES
I Explore potential biomarker indicators of response and resistance in AML samples
II To determine the measurable residual disease negative MRD response CRCri and its relation to CRCri status out of the total number of patients treated at each dose level of this regimen
III Determine number of patients that undergo hematopoietic stem cell transplant HSCT out of the total number of patients treated at each dose level of this regimen
IV Assess changes in OATP1B and CYP3A plasma biomarkers during treatment with SNDX-5613 with or without antifungal agents
V Determine duration of response
OUTLINE This is a phase Ib dose-escalation study of revumenib followed by a dose-expansion study
INDUCTION Patients receive revumenib orally PO every 12 hours Q12h on days 2-28 daunorubicin intravenously IV over 15 to 30 minutes on days 1-3 and cytarabine by continuous IV infusion CIV on days 1-7 in the absence of disease progression or unacceptable toxicity Patients who achieve a response to Induction treatment continue to Consolidation treatment Patients with persistent disease continue to Re-Induction treatment Patients also undergo a transthoracic echocardiogram ECHO or multigated acquisition scan MUGA during screening bone marrow aspiration and biopsy during screening and at the end of Induction and collection of blood during screening on days 2 3 15 and at the end of Induction
RE-INDUCTION Patients receive revumenib PO Q12h on days 2-28 daunorubicin IV over 15 to 30 minutes on days 1-2 and cytarabine CIV on days 1-5 in the absence of disease progression or unacceptable toxicity Patients who achieve a response to Re-Induction treatment continue to Consolidation Patients also undergo a transthoracic ECHO or MUGA on day 1 and bone marrow aspiration and biopsy at the end of Re-Induction
CONSOLIDATION Patients receive revumenib PO Q12h on days 2-28 and cytarabine CIV on days 1-3 in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy at the end of Consolidation and collection of blood on days 2 3 15 and at the end of Consolidation
After completion of study treatment patients are followed for 30 days or until death whichever occurs first
I To determine the maximum tolerated dose MTD recommended phase 2 dose RP2D and safety of revumenib SNDX-5613 combined with 7 3 induction in newly diagnosed untreated NPM1-mutatedFLT3-ITD wild type and NPM1-mutatedFLT3-TKD wild type or MLLKMT2A-rearranged acute myeloid leukemia AML patients 18-75 years old who are candidates for intensive induction therapy
II To determine the maximum tolerated dose MTD recommended phase 2 dose RP2D and safety of SNDX-5613 combined with one cycle of consolidation with high dose cytarabine in newly diagnosed AML patients in complete responsecomplete response with incomplete count recovery CRCri after intensive induction therapy with 73 for NPM1-mutatedFLT3-ITD wild type and NPM1-mutatedFLT3-TKD wild type or MLL KMT2A-rearranged AML patients 18-75 years old who are candidates for intensive therapy
SECONDARY OBJECTIVES
I Evaluate the pharmacokinetics of SNDX-5613 with this combination regimen and characterize clinically relevant drug-drug interactions with antifungal agents
II To determine the number of patients with CRCRi out of the total number of patients treated at each dose level of this regimen
EXPLORATORY OBJECTIVES
I Explore potential biomarker indicators of response and resistance in AML samples
II To determine the measurable residual disease negative MRD response CRCri and its relation to CRCri status out of the total number of patients treated at each dose level of this regimen
III Determine number of patients that undergo hematopoietic stem cell transplant HSCT out of the total number of patients treated at each dose level of this regimen
IV Assess changes in OATP1B and CYP3A plasma biomarkers during treatment with SNDX-5613 with or without antifungal agents
V Determine duration of response
OUTLINE This is a phase Ib dose-escalation study of revumenib followed by a dose-expansion study
INDUCTION Patients receive revumenib orally PO every 12 hours Q12h on days 2-28 daunorubicin intravenously IV over 15 to 30 minutes on days 1-3 and cytarabine by continuous IV infusion CIV on days 1-7 in the absence of disease progression or unacceptable toxicity Patients who achieve a response to Induction treatment continue to Consolidation treatment Patients with persistent disease continue to Re-Induction treatment Patients also undergo a transthoracic echocardiogram ECHO or multigated acquisition scan MUGA during screening bone marrow aspiration and biopsy during screening and at the end of Induction and collection of blood during screening on days 2 3 15 and at the end of Induction
RE-INDUCTION Patients receive revumenib PO Q12h on days 2-28 daunorubicin IV over 15 to 30 minutes on days 1-2 and cytarabine CIV on days 1-5 in the absence of disease progression or unacceptable toxicity Patients who achieve a response to Re-Induction treatment continue to Consolidation Patients also undergo a transthoracic ECHO or MUGA on day 1 and bone marrow aspiration and biopsy at the end of Re-Induction
CONSOLIDATION Patients receive revumenib PO Q12h on days 2-28 and cytarabine CIV on days 1-3 in the absence of disease progression or unacceptable toxicity Patients also undergo bone marrow aspiration and biopsy at the end of Consolidation and collection of blood on days 2 3 15 and at the end of Consolidation
After completion of study treatment patients are followed for 30 days or until death whichever occurs first
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-2023-04141 | REGISTRY | None | None |
| 10596 | OTHER | None | None |
| 10596 | OTHER | None | None |
| UM1CA186712 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186712 |