Ignite Creation Date:
2025-12-24 @ 2:50 PM
Ignite Modification Date:
2026-02-01 @ 6:31 PM
Study NCT ID:
NCT06504459
Status:
RECRUITING
Last Update Posted:
2025-08-27
First Post:
2024-07-11
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML
Sponsor:
OHSU Knight Cancer Institute
Organization:
Study Overview
Official Title:
A Phase II Study of Venetoclax (ABT-199) in Combination With Cladribine and Low-Dose Cytarabine Alternating With Azacitidine Plus Venetoclax in Newly Diagnosed Monocytic AML and Active-Signaling Mutated AML
Status:
RECRUITING
Status Verified Date:
2025-08
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 II trial tests how well venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax works in treating patients with newly diagnosed monocytic acute myeloid leukemia (AML) and active signaling mutated AML. 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. Chemotherapy drugs, such as cladribine, cytarabine and azacitidine, 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 venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed monocytic AML and active signaling mutated AML.
Detailed Description:
PRIMARY OBJECTIVE:
I. Assess efficacy of the investigational treatment based on disease remission.
SECONDARY OBJECTIVES:
I. Assess efficacy of the investigational treatment based on clinical response. II. Assess any-cause survival after treatment. III. Assess survival in the absence of treatment failure, hematologic relapse, or progressive disease.
IV. Assess duration of response, based on morphological assessments. V. Assess the safety and tolerability of the regimen.
EXPLORATORY OBJECTIVES:
I. Assess response based on measurable residual disease (MRD). II. Identify markers of clonal or clinical response and resistance to treatment.
III. Assess participant quality of life (QoL) using Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO CTCAE).
OUTLINE:
INDUCTION: Patients receive cladribine intravenously (IV) over 1-2 hours on days 1-5, cytarabine subcutaneously (SC) twice daily (BID) on days 1-10, and venetoclax orally (PO) once daily (QD) on days 1-21 of cycle 1.
RE-INDUCTION: Patients with \> 5% blasts after cycle 1 receive cladribine IV over 1-2 hours on days 1-5, cytarabine SC BID on days 1-10, and venetoclax PO QD on days 1-21 of cycle 2.
REMISSION AFTER INDUCTION: Patients who achieve complete remission (CR)/CR with partial hematologic recovery/CR with incomplete blood count recovery/morphologic leukemia-free state (MLFS) after cycle 1 of induction, receive cladribine IV over 1-2 hours on days 1-3, cytarabine SC BID on days 1-10 and venetoclax PO QD on days 1-21 of cycle 2.
CONTINUING THERAPY: Patients who achieve MLFS receive venetoclax PO QD on days 1-21 and azacitidine IV or SC QD on days 1-7 for 2 cycles then cladribine IV over 1-2 hours on days 1-3, cytarabine SQ BID on days 1-10 and venetoclax PO QD on days 1-21 for 2 cycles. Cycles repeat every 28 days and continue to alternate every 2 cycles for up to cycle 18 in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) as clinically indicated on study. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
At completion of study treatment, patients are followed up for 2 years.
I. Assess efficacy of the investigational treatment based on disease remission.
SECONDARY OBJECTIVES:
I. Assess efficacy of the investigational treatment based on clinical response. II. Assess any-cause survival after treatment. III. Assess survival in the absence of treatment failure, hematologic relapse, or progressive disease.
IV. Assess duration of response, based on morphological assessments. V. Assess the safety and tolerability of the regimen.
EXPLORATORY OBJECTIVES:
I. Assess response based on measurable residual disease (MRD). II. Identify markers of clonal or clinical response and resistance to treatment.
III. Assess participant quality of life (QoL) using Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO CTCAE).
OUTLINE:
INDUCTION: Patients receive cladribine intravenously (IV) over 1-2 hours on days 1-5, cytarabine subcutaneously (SC) twice daily (BID) on days 1-10, and venetoclax orally (PO) once daily (QD) on days 1-21 of cycle 1.
RE-INDUCTION: Patients with \> 5% blasts after cycle 1 receive cladribine IV over 1-2 hours on days 1-5, cytarabine SC BID on days 1-10, and venetoclax PO QD on days 1-21 of cycle 2.
REMISSION AFTER INDUCTION: Patients who achieve complete remission (CR)/CR with partial hematologic recovery/CR with incomplete blood count recovery/morphologic leukemia-free state (MLFS) after cycle 1 of induction, receive cladribine IV over 1-2 hours on days 1-3, cytarabine SC BID on days 1-10 and venetoclax PO QD on days 1-21 of cycle 2.
CONTINUING THERAPY: Patients who achieve MLFS receive venetoclax PO QD on days 1-21 and azacitidine IV or SC QD on days 1-7 for 2 cycles then cladribine IV over 1-2 hours on days 1-3, cytarabine SQ BID on days 1-10 and venetoclax PO QD on days 1-21 for 2 cycles. Cycles repeat every 28 days and continue to alternate every 2 cycles for up to cycle 18 in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) as clinically indicated on study. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
At completion of study treatment, patients are followed up for 2 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?: