Azacitidine + Venetoclax + Gilteritinib for Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase I/II trial studies the side effects and best dose of gilteritinib and to see how well it works in combination with azacitidine and venetoclax in treating patients with FLT3-mutation positive acute myeloid leukemia, chronic myelomonocytic leukemia, or high-risk myelodysplastic syndrome/myeloproliferative neoplasm that has come back (recurrent) or has not responded to treatment (refractory). Drugs used in chemotherapy, such as azacitidine, 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 may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine, venetoclax, and gilteritinib may work better compared to azacitidine and venetoclax alone in treating patients with acute myeloid leukemia, chronic myelomonocytic leukemia, or myelodysplastic syndrome/myeloproliferative neoplasm.
Is the combination of Azacitidine, Venetoclax, and Gilteritinib safe for humans?
Venetoclax has an acceptable safety profile for patients with certain types of leukemia, and Gilteritinib is a standard therapy for specific leukemia mutations. The combination of these drugs has been studied in patients with acute myeloid leukemia, showing potential safety and response, although specific safety data for the exact combination with Azacitidine is limited.
12357Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you should avoid certain drugs like carbamazepine, phenytoin, rifampin, and St. John's wort within 3 days of starting the study. It's best to discuss your current medications with the study team to ensure safety and compatibility.
What makes the drug combination of Azacitidine, Venetoclax, and Gilteritinib unique for treating leukemia?
This drug combination is unique because it combines three different agents: Azacitidine, which is a hypomethylating agent, Venetoclax, a B-cell lymphoma-2 inhibitor, and Gilteritinib, a FLT3 inhibitor, potentially offering a more comprehensive approach to treating acute myeloid leukemia, especially in patients who are older or have other health issues that make them ineligible for standard chemotherapy.
368910What data supports the effectiveness of the drug combination Azacitidine, Venetoclax, and Gilteritinib for leukemia?
Research shows that the combination of Venetoclax and Azacitidine improves remission rates and survival in older or unfit patients with acute myeloid leukemia compared to Azacitidine alone. Additionally, the combination significantly prolonged overall survival in patients ineligible for intensive chemotherapy.
34689Eligibility Criteria
Adults over 18 with FLT3-mutated acute myeloid leukemia, chronic myelomonocytic leukemia, or high-risk myelodysplastic syndrome/myeloproliferative neoplasm that's recurrent or refractory. Participants need a performance status of <=3 on the ECOG scale and adequate liver and kidney function. Exclusions include long QT syndrome, active central nervous system leukemia, HIV/hepatitis B/C infection, pregnancy/breastfeeding women, and those unwilling to use contraception.Inclusion Criteria
My leukemia has FLT3 mutations.
I am an adult with newly diagnosed AML that has a FLT3 mutation.
I can take care of myself but can't do heavy physical work.
I can swallow normally.
I am an adult with a specific type of leukemia or myelodysplastic syndrome that is considered high-risk.
Exclusion Criteria
I am HIV positive.
My leukemia has spread to my brain or spinal cord.
I have an ongoing serious infection that isn't getting better with antibiotics.
I do not have severe heart failure.
Participant Groups
The trial is testing how well gilteritinib works with azacitidine and venetoclax in treating certain blood cancers with FLT3 mutation. It aims to find the best dose of gilteritinib for effectiveness when combined with these chemotherapy drugs compared to using azacitidine and venetoclax alone.
1Treatment groups
Experimental Treatment
Group I: Treatment (azacitidine, venetoclax, gilteritinib)Experimental Treatment3 Interventions
Patients receive azacitidine SC or IV over 30-60 minutes on days 1-7, venetoclax PO QD on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles, and gilteritinib PO QD on days 1-28. Treatment of azacytidine and venetoclax repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Cycles of gilteritinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Azacitidine is already approved in European Union, United States, Canada, Japan, Australia for the following indications:
🇪🇺 Approved in European Union as Vidaza for:
- Acute myeloid leukemia
- Chronic myelomonocytic leukemia
- Myelodysplastic syndromes
🇺🇸 Approved in United States as Vidaza for:
- Myelodysplastic syndromes
- Chronic myelomonocytic leukemia
🇨🇦 Approved in Canada as Vidaza for:
- Myelodysplastic syndromes
- Acute myeloid leukemia
🇯🇵 Approved in Japan as Vidaza for:
- Myelodysplastic syndromes
- Acute myeloid leukemia
🇦🇺 Approved in Australia as Vidaza for:
- Myelodysplastic syndromes
- Acute myeloid leukemia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]Venetoclax is a selective, potent, first-in-class B-cell lymphoma-2 inhibitor that restores apoptosis in cancer cells and has demonstrated efficacy in a variety of hematological malignancies.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). .
Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities.
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.
Rapid and Efficient Response to Gilteritinib and Venetoclax-Based Therapy in Two AML Patients with FLT3-ITD Mutation Unresponsive to Venetoclax Plus Azacitidine. [2022]The presence of FLT3-ITD mutation is associated with relapse and poor survival in AML patients. Venetoclax combined with hypomethylating agents (VEN+HMA) was approved for the frontline treatment of elderly or unfit AML patients, which leads to noteworthy impacts on AML management. The combination therapy is associated with encouraging efficacy in FLT3-mutated AML among both newly diagnosed unfit and relapsed/refractory patients. However, we found that two AML patients with FLT3-ITD mutation did not respond to venetoclax plus azacitidine (VEN+AZA). Given that the combined efficacy of venetoclax and the FLT3 inhibitor has been proved in pre-clinical models of FLT3+ AML, it is a scientific rationale to investigate venetoclax combined with the FLT3 inhibitor in AML patients with FLT3-ITD mutation. This is the first report of assessing the safety and response of gilteritinib (the first and only targeted second-generation FLT3 tyrosine kinase inhibitor approved by the US FDA) and venetoclax-based therapy in two AML patients with FLT3-ITD mutation unresponsive to VEN+AZA, which may bring new hope to FLT3 mutated patients who are unresponsive to VEN+HMA.
Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. [2023]The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.
Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. [2023]Label="PURPOSE">The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory FLT3-mutated (FLT3mut) acute myeloid leukemia (AML) but seldom reduces FLT3mut burden or induces sustained efficacy. Gilteritinib combines synergistically with the BCL-2 inhibitor venetoclax in preclinical models of FLT3mut AML.
SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. [2023]Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN.
TP53 or Not TP53: That Is the Question. [2023]Azacitidine and venetoclax are a standard first-line regimen for patients with newly diagnosed unfit acute myeloid leukemia (AML). In a pooled subset analysis, TP53-mutated AML with poor-risk cytogenetics does not appear to benefit from the addition of venetoclax to azacitidine. This has clinical implications as these patients should be preferentially treated with alternative regimens. See related article by Pollyea et al., p. 5272.
Administration of combined venetoclax and azacitidine in a patient with acute myeloid leukemia and multiple comorbidities undergoing dialysis: A case report. [2023]Patients with acute myeloid leukemia (AML) who have comorbidities have limited treatment options, thereby resulting in poor prognosis. Venetoclax, a specific B-cell lymphoma-2 inhibitor, has recently been approved for AML in combination with hypomethylating agents; however, only one report has described its use in patients undergoing dialysis. Herein, we report the effectiveness of combined venetoclax and azacitidine in a 73-year-old man with AML undergoing dialysis and who was ineligible for standard therapies. The safety of venetoclax and azacitidine in patients undergoing dialysis has been reported, and their combination may be a feasible option for patients with AML undergoing dialysis.