NCT07228273

Induction and Consolidation With Fludarabine, Cytarabine, Idarubicin, and Venetoclax for the Treatment of Acute Myeloid Leukemia

A Phase II Randomized Clinical Trial of Venetoclax Combined With FLAG IDA Induction and Consolidation Compared to Standard of Care for Newly Diagnosed Patients With Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 102 (estimated)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, and daunorubicin, 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. 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 fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.

Detailed description

PRIMARY OBJECTIVE: I. Assess the efficacy of treatment based on rates of measurable residual disease negative composite complete remission (CRc-MRD-) determined using multiparameter flow cytometry (MFC). SECONDARY OBJECTIVES: I. Assess the efficacy of treatment based on complete response (CR) disease remission. II. Assess the efficacy of treatment based on overall clinical response. III. Assess the safety of treatment. IV. Assess survival in the absence of treatment failure, hematologic relapse, or progressive disease. V. Assess patient survival after commencing study therapy. VI. Assess the delay in hematopoietic stem cell transplant (HSCT) referral and consultation for transition to HSCT. VII. Assess the efficacy of treatment based on transitioning to HSCT. VIII. Assess disease response after transplant among participants who proceed to HSCT. IX. Assess risk of post-transplant infection among participants who proceed to HSCT. X. Assess risk of post-transplant graft versus host disease (GVHD) among participants who proceed to HSCT. XI. Assess survival in the absence of post-HSCT GVHD and relapse among participants who proceed to HSCT. EXPLORATORY OBJECTIVES: I. Evaluate the depth of response with measurable residual disease (MRD) testing and compare methods of determining MRD status. II. Evaluate survival of measurable residual disease negative (MRD-) patients with CR versus CR with partial or incomplete hematologic recovery. III. Assess participant quality of life (QoL) using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30). OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: INDUCTION: Patients receive fludarabine intravenously (IV) over 30 minutes and cytarabine IV over 4 hours on days 2, 3, 4, 5, and 6, idarubicin IV over 15-30 minutes on days 4, 5, and 6, and venetoclax orally (PO) once daily (QD) on days 3-9 of each cycle. Cycles repeat every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. Patients achieving CR, CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS) after one induction cycle proceed to consolidation. Patients achieving partial response (PR) after one induction cycle may proceed to consolidation at the investigator's discretion. Patients with ≥ 5% blasts after one cycle of induction may receive a second cycle of induction therapy. CONSOLIDATION: Patients receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 2, 3, and 4 of each cycle, idarubicin IV over 15-30 minutes on days 4, 5, and 6 of either cycles 3 and 6 or cycles 4 and 7, and venetoclax PO QD on days 3-9 of each cycle. Cycles repeat every 28 days for up to 6 post-induction cycles in the absence of disease progression or unacceptable toxicity. ARM 2: INDUCTION: Patients receive cytarabine IV on days 1-7 and daunorubicin IV on days 1-3 of each cycle. Cycles repeat every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. Patients achieving CR, CRh, CRi, or MLFS after one induction cycle proceed to consolidation. Patients achieving PR after one induction cycle may proceed to consolidation at the investigator's discretion. Patients with ≥ 5% blasts after one induction cycle may receive a second cycle of induction therapy. CONSOLIDATION: Participants receive cytarabine IV over 3 hours twice daily (BID) on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for up to 4 post-induction cycles in the absence of disease progression or unacceptable toxicity. Additionally, all patients undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening and on study as clinically indicated. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Cytarabine	Given IV
DRUG	Daunorubicin	Given IV
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Fludarabine	Given IV
DRUG	Idarubicin	Given IV
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA scan
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2025-12-12
• Primary completion: 2029-06-24
• Completion: 2029-08-24
• First posted: 2025-11-14
• Last updated: 2026-01-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study