Venetoclax + Azacitidine for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: CYP3A inducers
Disqualifiers: APL, FLT3-mutated AML, CML, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This research is being done to assess the therapeutic activity of a promising combination (azacitidine and venetoclax) versus conventional cytotoxic chemotherapy in induction-eligible patients with acute myeloid leukemia.
This study involves the following:
* Venetoclax and azacitidine (investigational combination)
* Cytarabine and idarubicin or daunorubicin (per standard of care) or Liposomal daunorubicin and cytarabine (per standard of care)
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does exclude patients who have taken strong or moderate CYP3A inducers within 7 days before starting the study treatment. It's best to discuss your current medications with the study team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination Venetoclax and Azacitidine for treating acute myeloid leukemia?
Research shows that the combination of Venetoclax and Azacitidine significantly improves survival and remission rates in patients with acute myeloid leukemia who are not eligible for intensive chemotherapy, compared to Azacitidine alone.
12345Is the combination of Venetoclax and Azacitidine safe for treating acute myeloid leukemia?
The combination of Venetoclax and Azacitidine has been studied for safety in patients with acute myeloid leukemia. Common side effects include blood-related issues, but the treatment is generally considered safe for older patients or those who cannot undergo intensive chemotherapy.
23467What makes the drug combination of Venetoclax and Azacitidine unique for treating acute myeloid leukemia?
The combination of Venetoclax and Azacitidine is unique because it is specifically used for older patients or those who cannot undergo intensive chemotherapy, offering improved remission rates and survival compared to Azacitidine alone.
12478Eligibility Criteria
Adults diagnosed with newly confirmed acute myeloid leukemia (AML), either de novo or secondary, who are eligible for intensive chemotherapy. Participants must be over 18, have an ECOG performance status ≤2, adequate liver function and heart health, and not have received prior AML treatment except hydroxyurea for cytoreduction. They must agree to use contraception due to unknown effects of venetoclax on fetuses.Inclusion Criteria
I haven't had cancer treatment for AML, except possibly hydroxyurea or ATRA.
Left ventricular ejection fraction > 50% as measured by echocardiogram or MUGA scan
Ability to understand and the willingness to sign a written informed consent document.
+10 more
Exclusion Criteria
My AML is FLT3-mutated.
I am under 60 and have AML with an NPM1 mutation.
I refuse blood products or am allergic to them.
+22 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either the investigational combination of venetoclax and azacitidine or standard induction chemotherapy with cytarabine and idarubicin (or daunorubicin) or liposomal daunorubicin and cytarabine.
Up to 3 years
Regular visits as per protocol
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of event-free survival and overall survival.
3 years
Consolidation (if needed)
Participants may receive additional cycles of chemotherapy to consolidate response, depending on age and response to initial treatment.
Varies
Participant Groups
The trial is testing the effectiveness of a combination therapy using azacitidine and venetoclax against standard induction chemotherapy options like cytarabine with idarubicin or daunorubicin, or liposomal daunorubicin and cytarabine in patients with acute myeloid leukemia.
2Treatment groups
Experimental Treatment
Group I: Standard of Care (Conventional Induction)Experimental Treatment4 Interventions
Randomized participants will receive cytarabine and idarubicin \[or daunorubicin) per standard of care as follows:
Induction: cytarabine on days 1-7 and idarubicin (or daunorubicin) on days 1-3 of induction.
Second Induction (if needed): Cytarabine on days 1-5 and idarubicin (or daunorubicin) on days 1-2 of re-induction.
Consolidation (if needed): If \< 60 years, cytarabine days 1,3,5 of consolidation cycles, and if ≥60 years, cytarabine days 1-5 of consolidation cycles
Those with secondary or therapy-related AML can receive liposomal daunorubicin and cytarabine (Vyxeos) per standard of care as follows:
Induction: Liposomal daunorubicin and cytarabine (Vyxeos) on Days 1,3, 5 of induction.
Second Induction (if needed): Liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of re-induction Consolidation (if needed): liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of consolidation cycles
Group II: Investigational (Venetoclax and Azacitidine)Experimental Treatment2 Interventions
Participants will receive azacitidine on days 1-7 and venetoclax daily for up to (3) three 28-day study cycles and evaluated for response or benefit. If benefit/response is achieved, azacitidine on days 1-7 and venetoclax on days 1-28 (or less if deemed necessary per protocol) will be given in repeating 28-day cycles until benefit/response is no longer achieved or until patient proceeds to transplantation.
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:
Massachusetts General Hospital Cancer CenterBoston, MA
University of California - DavisSacramento, CA
Ohio State University Medical CenterColumbus, OH
Dana-Farber Cancer InstituteBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
AbbVieIndustry Sponsor
References
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.
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-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.
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.
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.
Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. [2023]To retrospectively analyze the efficacy and safety of venetoclax combined with azacitidine (VEN + AZA) in the treatment of elderly patients with acute myeloid leukemia. The clinical data for 57 AML patients treated with the VEN + AZA regimen from December 2019 to November 2022 in the Department of Hematology, General Hospital of Tianjin Medical University, were collected. Of the 57 patients included in this study, the mean age of onset was 69.89 (±8.88) years. The median follow-up time was 8.57 months, and the median OS time was 11.50 months. The ORR, CR rate, and MRD (
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.
Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. [2022]Venetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is