Venetoclax in Combination With Decitabine in r/r AML
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|ClinicalTrials.gov Identifier: NCT03404193|
Recruitment Status : Recruiting
First Posted : January 19, 2018
Last Update Posted : December 12, 2019
The goal of this clinical research study is to learn if venetoclax in combination with decitabine can help to control acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) in newly diagnosed elderly patients or in patients with disease that has relapsed (come back after treatment). The safety of this drug combination will also be studied.
This is an investigational study. Venetoclax and decitabine are FDA approved and commercially available. Venetoclax is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia. Decitabine is FDA approved and commercially available for the treatment of MDS. It is considered investigational to use venetoclax in combination with decitabine to treat AML or HR-MDS.
The study doctor can explain how the study drugs are designed to work.
Up to 280 participants will be enrolled in this study. All will take part at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Blasts 10 Percent or More of Bone Marrow Nucleated Cells Blasts 10-20 Percent of Bone Marrow Nucleated Cells Chronic Myelomonocytic Leukemia High Risk Chronic Myelomonocytic Leukemia High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome Recurrent Acute Biphenotypic Leukemia Recurrent Acute Myeloid Leukemia Recurrent Chronic Myelomonocytic Leukemia Recurrent High Risk Myelodysplastic Syndrome Recurrent Mixed Phenotype Acute Leukemia Refractory Acute Myeloid Leukemia Refractory Chronic Myelomonocytic Leukemia Refractory High Risk Myelodysplastic Syndrome Refractory Mixed Phenotype Acute Leukemia TP53 Gene Deletion TP53 Gene Mutation||Drug: Decitabine Other: Laboratory Biomarker Analysis Drug: Venetoclax||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||280 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||January 16, 2018|
|Estimated Primary Completion Date :||December 30, 2020|
|Estimated Study Completion Date :||December 30, 2021|
Experimental: Treatment (decitabine, venetoclax)
Participants receive decitabine by vein 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 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.
20 mg/m2 by vein over approximately 1 hour daily x 10 days on days 1-10 of each treatment cycle.
Other: Laboratory Biomarker Analysis
400 mg by mouth on Days 1-28 of the first cycle and Days 1-21 of all other cycles.
- Overall response rate (ORR) of venetoclax in combination with 10-day decitabine [ Time Frame: 3 months ]ORR defined as the proportion of patients who had CR (complete remission), CRp (complete remission with incomplete platelet recovery), CRi (complete remission with incomplete count recovery), PR (partial response) or marrow clearance of blasts within 3 months of treatment initiation among adult patients with AML; and complete remission (CR), partial remission (PR) or marrow CR† (mCR) lasting at least 4 weeks for patients with MDS.
- Duration of Response of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
- Disease-Free Survival (DFS) of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
- Overall Survival (OS) of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
- Determination of 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. [ Time Frame: 1 year ]
- Safety of venetoclax in combination with 10-day decitabine in patients with refractory/ relapsed AML. [ Time Frame: Baseline up to 30 days after last dose of study drug ]The overall incidence and severity of all reported adverse events using Common Toxicity Criteria v 4.0.
- Determination of the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day decitabine regimen. [ Time Frame: 3 months ]Response assessed based by Modified IWG Response Criteria for MDS (Cheson et al, 2006).
- Determine the incidence of infections complications per cycle with the Venetoclax in combination with 10-day Decitabine. [ Time Frame: 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03404193
|Contact: Marina Konopleva, MD, PHDfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Marina Konopleva 713-794-1628|
|Principal Investigator: Marina Konopleva|
|Principal Investigator:||Marina Konopleva||M.D. Anderson Cancer Center|