NCT03404193

Venetoclax and Decitabine in Treating Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed High-Risk Myelodysplastic Syndrome

A Phase II Study of Venetoclax in Combination With 10-Day Decitabine in Newly Diagnosed Elderly or Relapsed/Refractory Acute Myeloid Leukemia and Relapsed High-Risk Myelodysplastic Syndrome and Blastic Plasmacytoid Dendritic Cell Neoplasm

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 235 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well venetoclax and decitabine work in treating participants with acute myeloid leukemia that has come back or does not respond to treatment, or with high-risk myelodysplastic syndrome that has come back. Drugs used in chemotherapy, such as venetoclax and decitabine, 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.

Detailed description

PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) of venetoclax in combination with 10-day decitabine in patients with refractory/relapsed acute myeloid leukemia (AML); elderly (\> 60 year old) patients with newly diagnosed AML not eligible for intensive chemotherapy; patients with high-risk myelodysplastic syndrome (MDS) with bone marrow blasts between 10% and 20%, relapsed or refractory to prior hypomethylating agent (HMA) therapy, or chronic myelomonocytic leukemia (CMML) with bone marrow blasts \>= 10% regardless of prior therapy; AML patients with prior history of MDS or CMML who received therapy for the MDS or CMML and progressed to AML, and younger patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations and patients with blastic plasmacytoid dentritic cell neoplasm (BPDCN). SECONDARY OBJECTIVES: I. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination. II. To determine the number of patients who achieve a hematologic improvement (HI) in platelets, hemoglobin, or absolute neutrophil count (ANC) and the number of patients who achieve \> 50% reduction in blasts on therapy with venetoclax/10-day decitabine. III. To determine the safety of venetoclax in combination with 10-day decitabine in patients with refractory/relapsed AML. IV. To determine the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day decitabine regimen. V. To determine the incidence of infectious complications per cycle with venetoclax in combination with 10-day decitabine. EXPLORATORY OBJECTIVES: I. To investigate possible relationships between baseline protein and gene expression signatures/mutation profile and BH3 profiling in predicting clinical response to the combination. II. To characterize the pharmacokinetic (PK) profiles of venetoclax in combination with decitabine and antifungals in plasma samples. OUTLINE: Participants receive decitabine intravenously (IV) over 1 hour on days 1-10 and may also receive decitabine on days 1-5 after achieving complete remission/complete remission with incomplete count recovery during consolidation/maintenance. Participants also receive venetoclax orally (PO) daily on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles. Treatment repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up every 3 to 6 months for up to 5 years.

Conditions

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Chronic Myelomonocytic Leukemia
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndrome
• Recurrent Acute Biphenotypic Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm
• Recurrent Chronic Myelomonocytic Leukemia
• Recurrent Mixed Phenotype Acute Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm
• Refractory Chronic Myelomonocytic Leukemia
• Refractory Mixed Phenotype Acute Leukemia

Interventions

Type	Name	Description
DRUG	Decitabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2018-01-18
• Primary completion: 2026-03-05
• Completion: 2026-03-05
• First posted: 2018-01-19
• Last updated: 2026-03-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study