Combination Chemotherapy for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: Pregnancy, Uncontrolled illness, Hypersensitivity, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies how well cladribine, idarubicin, cytarabine, and venetoclax work in patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. Drugs used in chemotherapy, such as cladribine, idarubicin, cytarabine, 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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it allows prior use of certain drugs like hydroxyurea and azacytidine, suggesting some medications might be continued. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination for treating acute myeloid leukemia?
Research shows that adding venetoclax to other treatments like cladribine and low-dose cytarabine can improve remission rates and survival in older patients with acute myeloid leukemia. Another study found that venetoclax combined with low-dose cytarabine significantly improved remission rates and overall survival compared to low-dose cytarabine alone.
12345Is the combination chemotherapy for acute myeloid leukemia safe?
Venetoclax-based combinations for acute myeloid leukemia have been studied and are generally considered safe, though hematologic toxicities (blood-related side effects) are common. These combinations have been used effectively in both newly diagnosed and relapsed cases, with safety data available from studies conducted in various settings.
678910How is the drug combination of Cladribine, Idarubicin, and Venetoclax unique for treating acute myeloid leukemia?
This drug combination is unique because it includes Venetoclax, which is known to improve remission rates and survival in older or unfit patients with acute myeloid leukemia when combined with other drugs like azacitidine. Venetoclax works by targeting and inhibiting a protein that helps cancer cells survive, making it a novel addition to traditional chemotherapy regimens.
2461112Eligibility Criteria
This trial is for adults with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. Eligible participants must have certain levels of liver and kidney function, a heart ejection fraction >= 45%, an ECOG performance status of =< 2 (which means they can do some activities), and no severe allergies to the drugs used. Pregnant or breastfeeding women cannot join, and participants must agree to use contraception.Inclusion Criteria
I have been diagnosed with AML, acute biphenotypic leukemia, high risk MDS, or CML in myeloid blast phase.
I can take care of myself but might not be able to do heavy physical work.
A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial
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Exclusion Criteria
Pregnant women are excluded from this study due to potential teratogenic or abortifacient effects; breastfeeding should also be avoided
Patient with documented hypersensitivity to any of the components of the chemotherapy program
I am using contraception or agree to use it during the study.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction
Patients receive cladribine, cytarabine, and idarubicin intravenously, with additional treatments for specific mutations, repeated every 28 days for up to 2 cycles
8 weeks
Multiple visits for IV administration
Consolidation
Patients receive cladribine, cytarabine, and idarubicin intravenously, with additional treatments for specific mutations, repeated every 28 days for up to 5 cycles
20 weeks
Multiple visits for IV administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
6-12 months
Participant Groups
The study tests how well a combination of chemotherapy drugs—cladribine, idarubicin, cytarabine—and venetoclax work in treating specific blood cancers. It's designed to see if these drugs can stop cancer cells from growing by killing them or preventing their division and spread.
1Treatment groups
Experimental Treatment
Group I: Treatment (cladribine, cytarabine, idarubicin)Experimental Treatment7 Interventions
INDUCTION: Patients receive cladribine IV and cytarabine IV over 1-2 hours on days 1-5 and idarubicin IV over 30-60 minutes on days 1-3. Patients with untreated AML and MDS also receive venetoclax PO on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO BID on days 6-19 or gilteritinib PO QD on days 1-14. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive cladribine IV and cytarabine IV over 1-2 hours on days 1-3 and idarubicin IV over 30-60 minutes on days 1-2. Patients with untreated AML and MDS also receive venetoclax PO on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO BID on days 6-19 or gilteritinib PO QD. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
Cladribine is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Leustatin for:
- Hairy cell leukemia
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin's lymphoma
- Multiple sclerosis
🇪🇺 Approved in European Union as Litak for:
- Hairy cell leukemia
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin's lymphoma
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
Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. [2021]Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.
Fludarabine, cytarabine, and idarubicin with or without venetoclax in patients with relapsed/refractory acute myeloid leukemia. [2023]Treatment options for relapsed and refractory acute myeloid leukemia patients (R/R AML) are limited. This retrospective cohort study compares safety and efficacy of fludarabine, cytarabine, and idarubicin (FLA-IDA) with or without venetoclax in patients with R/R AML. Thirty-seven and 81 patients received one course FLA-IDA with or without a 7-day course of venetoclax, respectively. The overall response rate (ORR) was significantly higher in FLAVIDA compared to FLA-IDA treated patients (78% vs. 47%; P=0.001), while MRD was negative at a similar proportion in responding patients (50% vs. 57%), respectively. Eightyone percent and 79% of patients proceeded to allogeneic hematopoietic cell transplantation (alloHCT) or donor lymphocyte infusion (DLI) after FLAVIDA and FLA-IDA, respectively. Event-free and overall survival were similar in FLAVIDA and FLA-IDA treated patients. Refractory patients could be salvaged more successfully after FLA-IDA compared to FLAVIDA pretreatment. Neutrophil and platelet recovery times were similar in the venetoclax and the control group. In conclusion, short-term venetoclax in combination with FLA-IDA represents an effective treatment regimen in R/R AML identifying chemosensitive patients rapidly and inducing MRD negative remission in a high proportion of R/R AML patients.
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.
BCL2/MDM2 Inhibitor Combo Effective in AML. [2019]The BCL2 inhibitor venetoclax plus the MDM2 inhibitor idasanutlin may be effective in treating relapsed/refractory acute myeloid leukemia. In a phase Ib trial, 35.9% of patients who received the combination had a response; side effects were manageable.
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.
[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. [2023]To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML).
Comparative effectiveness of glasdegib versus venetoclax combined with low-dose cytarabine in acute myeloid leukemia. [2021]Background: Two combination therapies recently approved and recommended for use in combination with low-dose cytarabine (LDAC) in acute myeloid leukemia patients unfit for intensive chemotherapy are glasdegib+LDAC and venetoclax+LDAC. Materials & methods: An indirect treatment comparison used median overall survival, overall survival hazard ratios, complete remission (CR), CR+CR with incomplete blood count recovery and transfusion independence to assess comparative effectiveness, and a simulated treatment comparison accounted for differences in patient characteristics between trials. Results: Differences in efficacy between glasdegib+LDAC and venetoclax+LDAC were suggestive and not statistically significant. Conclusion: With no significant differences in comparative effectiveness, considerations such as safety profiles, burden of administration and patient preference are likely to guide treatment decisions.
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 combination therapy in acute myeloid leukemia and myelodysplastic syndromes. [2023]Venetoclax is a BCL-2 inhibitor that was approved in combination therapy with hypomethylating agents or low dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The purpose of this review is to outline the most recent venetoclax-based combination therapies in newly diagnosed or relapsed myelodysplastic syndrome (MDS) and AML 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.
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.