Navitoclax + Venetoclax + Decitabine for Myelodysplastic Syndrome
Trial Summary
What is the purpose of this trial?
This phase Ib/II trial tests the safety, side effects, and best dose of navitoclax in combination with venetoclax and decitabine in treating patients with higher risk myelodysplastic syndrome (MDS) that has come back after initial treatment or was not responsive to initial treatment. This study will also look at the effectiveness of the treatment combination and patient's quality of life while on these medications. Navitoclax is an oral drug that works as an inhibitor of the BCL-2 family of proteins, which are often overly expressed in a wide variety of cancers and are linked to tumor drug resistance. This drug blocks some of the enzymes that keep cancer cells from dying. Venetoclax is an oral drug that works as an inhibitor of BCL-2 proteins that works very similarly to navitoclax by blocking the action of a certain proteins in the body that helps cancer cells survive which helps to kill cancer cells. Decitabine is an intravenous drug. It is a hypomethylating agent which means it interferes with deoxyribonucleic acid (DNA) methylation. DNA methylation is a major factor that regulates gene expression in cells, and an increase in DNA methylation can block the genes that regulate cell division and growth. When these genes are blocked the overall result allows or promotes cancer as there is no control over cell growth. Decitabine stops cells from making DNA and may kill cancer cells. Participation in this trial may improve the understanding of both chemotherapy response in MDS and mechanisms of resistance to current therapies.
Will I have to stop taking my current medications?
The trial requires that you stop taking medications that interfere with blood clotting or platelet function, except for low-dose aspirin and certain blood thinners, which must be stopped at least 3 days before starting the trial. If you are on these medications and cannot stop, you will not be able to participate.
What data supports the effectiveness of the drug combination of Navitoclax, Venetoclax, and Decitabine for Myelodysplastic Syndrome?
Research shows that Venetoclax combined with Decitabine has been effective in treating acute myeloid leukemia (AML), especially in older patients or those who cannot undergo intensive chemotherapy. This combination has shown promising results in achieving remission and improving survival rates, suggesting potential benefits for similar blood disorders like Myelodysplastic Syndrome.12345
Is the combination of Navitoclax, Venetoclax, and Decitabine safe for humans?
The combination of Venetoclax and Decitabine has been studied for safety in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). It is generally considered safe, but it can cause side effects like myelosuppression (a decrease in blood cell production), which may be severe, especially in elderly or frail patients.12456
What makes the drug combination of Navitoclax, Venetoclax, and Decitabine unique for treating myelodysplastic syndrome?
This drug combination is unique because it combines Navitoclax, a BCL-2 family protein inhibitor, with Venetoclax, another BCL-2 inhibitor, and Decitabine, a hypomethylating agent, which may enhance the treatment's effectiveness by targeting cancer cells in different ways. This approach is novel compared to standard treatments that typically use only one or two of these components.14578
Eligibility Criteria
Adults with aggressive myelodysplastic syndrome (MDS) who have tried azacitidine or decitabine and venetoclax without success. They must be able to swallow pills, not pregnant or breastfeeding, willing to use contraception, and have an ECOG Performance Status of 0-2 indicating they are relatively active.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment Cycle 1
Participants receive navitoclax, venetoclax, and decitabine with bone marrow biopsy and blood sample collection
Treatment Cycle 2 and Beyond
Participants continue receiving navitoclax, venetoclax, and decitabine with bone marrow biopsy and blood sample collection
Follow-up
Participants are monitored for safety and effectiveness after treatment
Survival Follow-up
Participants are followed for overall survival
Treatment Details
Interventions
- Decitabine
- Navitoclax
- Venetoclax
Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:
- Acute myeloid leukemia
- Myelodysplastic syndromes
- Myelodysplastic syndromes
- Acute myeloid leukemia
- Myelodysplastic syndromes
- Acute myeloid leukemia
- Myelodysplastic syndromes
- Acute myeloid leukemia
Find a Clinic Near You
Who Is Running the Clinical Trial?
Thomas Jefferson University
Lead Sponsor
AbbVie
Industry Sponsor
Dr. Roopal Thakkar
AbbVie
Chief Medical Officer since 2023
MD from Wayne State University School of Medicine
Robert A. Michael
AbbVie
Chief Executive Officer
Bachelor's degree in Finance from the University of Illinois