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|
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Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive decitabine by vein over about 1 hour on Days 1-10 of each 28-day study cycle. Note that the start of future cycles may be delayed if you have side effects to the study drug.
You will take venetoclax by mouth on Days 1-28 of the first cycle and Days 1-21 of all other cycles. Each dose should be taken within 30 minutes after eating a meal (preferably breakfast) with about a cup (8 ounces) of water. If the study doctor thinks it is needed based on any side effects you may be having (such as low blood cell counts and/or infections), your dose(s) of venetoclax may be delayed until it is thought to be safe for you to receive it.
If venetoclax is not available at the start of treatment for any reason (insurance, financial, transportation, and so on), you can begin receiving decitabine and venetoclax can be added when it is available.
During Cycle 1, you will be admitted into the hospital as an inpatient for at least the first 3 days of combination therapy. During this time, you will also be given drugs to prevent tumor lysis syndrome (TLS). TLS happens when breakdown products of the cancer cells entering the blood stream, causing possible weakness, low blood pressure, muscle cramps, kidney damage, and/or other organ damage. You may be given fluids (either by mouth or by vein) and treatment with allopurinol or rasburicase. After Day 3, if there is If no evidence of TLS, you may be discharged. You will then receive the rest of the study drug doses as an outpatient.
If the study doctor thinks it is in your best interest, you may be able to also receive standard of care therapies (such as sorafenib, midostaurin, imatinib, dasatinib, ponatinib, and so on) while you are on study. The study doctor will discuss these treatments with you, as well as their risks and benefits.
If the study doctor thinks it is needed for your safety, you may also receive cytarabine to help prevent central nervous system side effects. Cytarabine will be given intrathecally (through a spinal tap) on either Day 21 of Cycle 1 or Day 14 of Cycle 2.
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
On Day 1 of each cycle (+/- 4 days), you will have a physical exam.
One (1) time every week during Cycles 1, 2 and 3, and then on Day 1 of each cycle after that (+/- 4 days):
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a bone marrow biopsy and aspirate to check the status of the disease, and for biomarker and cytogenetic testing (Day 21 [+/- 3 days]). If the study doctor thinks it is needed, this will be repeated on Day 28. Additionally, you will have a bone marrow biopsy and aspirate to check the status of the disease, for biomarker and for cytogenetic testing at the end of Cycles 2 and 4, then every 1-3 cycles after that, then at any time that the disease appears to get worse.
Additional Research Tests:
Blood (about 3 tablespoons) will be drawn for biomarker testing at the following time points (within 24 hours). Biomarkers, which may include genetic biomarkers, are found in the blood and tissue and may be related to your reaction to the study drug:
- Baseline (before the first decitabine dose), about Day 3 of Cycle 1, and between Days 21 to 28 of Cycle 1
- At the end of Cycles 2 and 4
- At any point that the disease appears to get worse
You will have a "cheek scrape" at the end of Cycle 1. These cells will be used to compare to cancer cells to look for effects of the study drug. For this test, a small sample of cells from the inside of your mouth will be collected by scraping a special brush against the inside of your cheek a few times, until enough cells are collected.
Within 30 days after your last dose of study drug(s):
- You will have a physical exam.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a bone marrow aspirate/biopsy to check the status of the disease and for biomarker and cytogenetic testing.
If the disease responded to the study treatment, you will then be called every 3 to 6 months for up to 5 years and asked about how you are doing. Each call should last about 15-30 minutes.
|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, PHDemail@example.com|
|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|