Quizartinib + Decitabine + Venetoclax for Acute Myeloid 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
Must not be taking: Strong CYP3A4 inhibitors
Disqualifiers: Uncontrolled CNS leukemia, Diabetes, Cardiovascular disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This phase I/II trial studies how well quizartinib, decitabine, and venetoclax work in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome that is untreated or has come back (relapsed). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine and venetoclax, 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. Giving quizartinib and decitabine may work better at treating acute myeloid leukemia and myelodysplastic syndrome.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect the heart's rhythm or strong CYP3A4 inhibitors (a type of enzyme that affects drug metabolism). It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination of Quizartinib, Decitabine, and Venetoclax for treating Acute Myeloid Leukemia?
Is the combination of Quizartinib, Decitabine, and Venetoclax safe for humans?
The combination of Venetoclax and Decitabine has been studied in patients with acute myeloid leukemia (AML), showing common side effects like nausea, diarrhea, constipation, and low blood cell counts, but it was generally well tolerated in elderly patients. No tumor lysis syndrome (a serious condition caused by the rapid breakdown of cancer cells) was observed, indicating a manageable safety profile.12567
What makes the drug combination of Quizartinib, Decitabine, and Venetoclax unique for treating acute myeloid leukemia?
This drug combination is unique because it includes Quizartinib, which targets a specific mutation in leukemia cells, alongside Decitabine and Venetoclax, which are used to treat older patients or those unable to undergo intensive chemotherapy. This combination may offer a new option for patients with specific genetic profiles or those who have not responded well to other treatments.2891011
Eligibility Criteria
This trial is for adults with untreated or relapsed Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS). Eligible participants include those over 60 not fit for intensive therapy, under 60 with poor risk factors, and must have specific genetic mutations. They should be able to take oral medication and not have severe medical conditions or allergies related to the drugs tested.Inclusion Criteria
I have not received chemotherapy for my condition.
I can take certain medications during the study.
I am generally healthy, can take pills, understand and agree to the study, not pregnant, and not on experimental drugs.
See 8 more
Exclusion Criteria
I have previously used quizartinib.
I do not have other severe illnesses or cancers.
Known allergy or hypersensitivity to specific components
See 12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive decitabine intravenously over 1 hour on days 1-10, quizartinib orally every day beginning on day 1 of cycle 1, and venetoclax orally on days 1-14 (days 1-21 if persistent leukemia). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
28 days per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment completion every 3-6 months for up to 5 years.
Up to 5 years
Treatment Details
Interventions
- Decitabine (DNA Methyltransferase Inhibitor)
- Quizartinib (FLT3 Inhibitor)
- Venetoclax (BCL-2 Inhibitor)
Trial OverviewThe study tests a combination of quizartinib, decitabine, and venetoclax in patients with AML/MDS. Quizartinib targets enzymes that cancer cells need to grow while decitabine and venetoclax are chemotherapy drugs aimed at stopping cancer cell growth by various mechanisms.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (decitabine, quizartinib, venetoclax)Experimental Treatment3 Interventions
Patients receive decitabine IV over 1 hour on days 1-10, quizartinib PO every day beginning on day 1 of cycle 1, and venetoclax PO on days 1-14 (days 1-21 if persistent leukemia). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Dacogen for:
- Acute myeloid leukemia
- Myelodysplastic syndromes
🇺🇸 Approved in United States as Dacogen for:
- Myelodysplastic syndromes
- Acute myeloid leukemia
🇨🇦 Approved in Canada as Dacogen for:
- Myelodysplastic syndromes
- Acute myeloid leukemia
🇯🇵 Approved in Japan as Dacogen 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
National Cancer Institute (NCI)Collaborator
References
Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. [2022]We report the efficacy and safety of venetoclax plus decitabine-based treatment in heavily pre-treated relapsed or refractory acute myeloid leukaemia (RR-AML) in a real-world setting.
Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. [2021]Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).
Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. [2022]Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p
Venetoclax in association with decitabine as effective bridge to transplant in a case of relapsed early T-cell lymphoblastic leukemia. [2020]A case of an early-relapsed high-risk T-ALL with high BCL-2 expression on leukemic blasts was successfully treated with decitabine and venetoclax, achieving a CR. We suggest decitabine and venetoclax should be synergistic in BCL2-positive ALL.
Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax. [2023]Label="BACKGROUND">TP53 mutation (TP53mut ) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10-day decitabine and venetoclax (DEC10-VEN) (ClinicalTrials.gov identifier NCT03404193).
10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. [2021]Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine that has shown promising results in patients with high-risk AML in phase 2 trials. We hypothesised that venetoclax with 10-day decitabine could have improved activity in patients with newly diagnosed AML and those with relapsed or refractory AML, particularly in high-risk subgroups.
[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]Objective: To investigate the effectiveness and safety of the VA regimen, which combines venetoclax with azacitidine in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for conventional chemotherapy. Methods: In the Department of Hematology at the Second Hospital of Hebei Medical University, 66 AML patients who received venetoclax and azacitidine treatment from May 2020 to March 2022 were the subject of a retrospective study. The complete remission (CR) rate, cCR rate, ORR rate, MRD negative rate, the incidence of adverse events,1-year EFS, and OS were retrospectively analyzed. Patients subgroups with varying ages, ECOG scores, primary and secondary, risk stratifications, and gene mutation were compared for differences in efficacy and survival. Results: The median follow-up was 4.25 (0.9-19.9) months, and the median number of treatment courses was 2 (1-8) cycles. After the first cycle, the cCR rate was 78.8% , and the MRD negative rate was 51.9% . After prolonged treatment, the cCR rate was 81.8% and MRD negative rate was 66.7% . The median EFS and OS, respectively, were13.2 and 15.3 months. Secondary AML showed inferior efficacy and prognosis. IDH1/2 or NPM1 mutation groups had a significantly higher rate of CR than the control group (P<0.05) . The CR rate and MRD negative rate of patients with rebound thrombocytosis were significantly higher than those without rebound thrombocytosis (P<0.05) . Those who had epigenetic modification mutations (DNMT3, ASXL1, TET2) were more likely to benefit from ongoing therapy. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia. Conclusions: In real-world patients with newly diagnosed AML who are not candidates for standard chemotherapy, the VA regimen produces rapid deep remission. Primary AML patients, rebound thrombocytosis, IDH1/2, and NPM1 gene mutations are favorable factors for treatment benefit, and adverse reactions were tolerable.
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.
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.
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.
Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. [2022]Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18-74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.