ASTX727 + Dasatinib for Chronic Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must be taking: Tyrosine kinase inhibitors
Disqualifiers: Heart disease, Psychiatric disorders, HIV, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial studies the effect of ASTX727 and dasatinib in treating patients with newly diagnosed Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in chronic phase. Philadelphia chromosome positive and BCR-ABL positive are types of genetic mutations (changes). Chemotherapy drugs, such as ASTX727, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 and dasatinib may help to control Philadelphia chromosome-positive chronic myeloid leukemia or BCR-ABL positive chronic myeloid leukemia in chronic phase.
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 mentions that participants should have received minimal prior therapy for chronic myeloid leukemia, defined as less than 1 month of certain medications. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination ASTX727 and Dasatinib for treating chronic myeloid leukemia?
Research shows that combining dasatinib with decitabine, a component of ASTX727, is safe and effective for advanced chronic myeloid leukemia, with nearly half of the patients achieving significant blood and genetic responses, and improved survival rates.
12345Is the combination of ASTX727 and Dasatinib safe for treating chronic myeloid leukemia?
The combination of dasatinib and decitabine (part of ASTX727) has been studied in patients with advanced chronic myeloid leukemia, showing it to be generally safe, though some patients experienced serious side effects like blood-related issues. Dasatinib alone has been used since 2005 and is known to cause side effects such as myelosuppression (reduced bone marrow activity) and pleural effusions (fluid around the lungs), but dose adjustments can help manage these.
12456How is the drug combination of ASTX727 and Dasatinib unique for treating chronic myeloid leukemia?
The combination of ASTX727 (Decitabine/Cedazuridine) and Dasatinib is unique because it combines a DNA methylation inhibitor with a tyrosine kinase inhibitor, potentially enhancing treatment effectiveness for advanced-phase chronic myeloid leukemia, where single-agent therapies have limited success.
12457Eligibility Criteria
This trial is for adults newly diagnosed with Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in the early chronic phase. They should have minimal prior treatment, good organ function, and an ECOG performance of 0-2. Pregnant women, those with serious heart disease, significant bleeding disorders, uncontrolled infections or hepatitis B/C are excluded.Inclusion Criteria
Total bilirubin < 1.5 x upper limit of normal (ULN) (unless secondary to Gilbert's disease, < 2.5 x ULN)
Patients must sign an informed consent indicating awareness of the investigational nature of the study
I can take care of myself and am up and about more than half of my waking hours.
+5 more
Exclusion Criteria
I do not have any uncontrolled mental health issues.
Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 460 msec)
My chronic myeloid leukemia is in an accelerated phase.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive dasatinib daily, and starting from cycle 4, also receive decitabine and cedazuridine for 3 days in each 28-day cycle
3 years
Maintenance
Participants continue to receive dasatinib daily in 28-day cycles
12 years
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
15 years
Follow-up at 30 days post-treatment, then every 6 months
Participant Groups
The trial is testing ASTX727 (a chemotherapy drug) combined with dasatinib (an enzyme blocker) to treat chronic myeloid leukemia. It aims to see if this combination can control cancer cell growth by killing cells or stopping them from dividing and spreading.
1Treatment groups
Experimental Treatment
Group I: Treatment (dasatinib, decitabine and cedazuridine)Experimental Treatment2 Interventions
Patients receive dasatinib PO QD on days 1-28. Beginning cycle 4, patients also receive decitabine and cedazuridine PO QD on days 1-3. Cycles repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days for up to 12 years in the absence of disease progression or unacceptable toxicity.
ASTX727 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Inqovi for:
- Myelodysplastic Syndromes (MDS)
🇪🇺 Approved in European Union as Inqovi for:
- Myelodysplastic Syndromes (MDS)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
Loading ...
Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
Astex Pharmaceuticals, Inc.Industry Sponsor
References
Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects. [2023]Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.
Metabolism and disposition of dasatinib after oral administration to humans. [2015]SPRYCEL (dasatinib, BMS-354825; Bristol-Myers Squibb, Princeton, NJ), a multiple kinase inhibitor, is currently approved to treat chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia tumors in patients who are resistant or intolerant to imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). After a 100-mg single p.o. dose of [(14)C]dasatinib to healthy volunteers, the radioactivity was rapidly absorbed (T(max) approximately 0.5 h). Both dasatinib and total radioactivity (TRA) plasma concentrations decreased rapidly with elimination half-life values of
The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. [2022]Decitabine (5-aza-2'-deoxycytidine) is a hypomethylating agent used in the treatment of acute myeloid leukemia (AML). Decitabine inhibits DNA methyltransferases, causing DNA hypomethylation, and leading amongst others to re-expression of silenced tumor suppressor genes. Decitabine is indicated for the treatment of adult patients with newly diagnosed de novo or secondary AML who are not eligible for standard induction chemotherapy. The initial authorization in 2012 was based on the results of the open-label, randomized, multicenter phase 3 DACO-016 trial, and supported by data from the supportive phase 2 open-label DACO-017 trial. Compared with standard care, decitabine significantly improved overall survival, event-free survival, progression-free survival, and response rate. Decitabine was generally well tolerated, offering a valuable treatment option in patients with AML irrespective of age, especially for patients achieving a complete response. Several observational "real-life" studies confirmed these results. In contrast to standard chemotherapy, the presence of adverse-risk karyotypes or TP53 mutations does not negatively impact sensitivity to hypomethylating therapy albeit with lower durability. Data suggest a potential positive effect of decitabine in patients with monosomal karyotype-positive AML. For the time being, decitabine is an appropriate option as monotherapy for patients with AML who are unfit to receive more intensive combination therapies, but emerging data suggest that decitabine-based doublet or triplet combinations may be future treatment options for patients with AML.
Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia. [2020]Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome positive acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematological adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematologic response and six (22%) achieved a minor hematologic response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major molecular response. Median overall survival (OS) was 13.8 months, with significantly higher OS among patients who achieved a hematologic response compared to non-responders (not reached vs 4.65 months; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted.
Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. [2023]On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval.
[Guidelines for the management of dasatinib (Sprycel)-induced side effects in chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemias]. [2015]Dasatinib (Sprycel) is a new-targeted therapy used since 2005 in the treatment of chronic myelogenous leukemia and de novo Philadelphia positive acute lymphoblastic leukaemia patients, intolerant or resistant to imatinib. Despite its high efficacy in such patients in terms of hematologic, cytogenetic and molecular responses, the onset of frequent and sometimes serious side effects particularly in advanced phase patients, especially myelosuppressions and pleural effusions, may impair optimal administration of the drug. Recently, dasatinib dose optimisation in chronic-phase has reduced the incidence of such adverse events without modification of the efficacy, however, their optimal overall management can efficiently reduce their severity and minimize their impact on disease response. Hereby, we attempted to propose a series of guidelines that might be of help in daily practice, in order to control properly these side effects.
A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. [2022]Tyrosine kinase inhibitor therapy with imatinib (IM), dasatinib (DAS), or nilotinib is very effective in chronic-phase chronic myeloid leukemia. Two hundred fifty-three patients with newly diagnosed chronic-phase chronic myeloid leukemia were randomized to IM 400 mg/day or DAS 100 mg/day. The proportion of patients achieving a complete cytogenetic remission rate was superior with DAS (84% vs 69%), as was the 12-month molecular response by the proportions of patients achieving > 3-log, > 4-log, and > 4.5-log reduction in BCR-ABL transcript levels. Overall and progression-free survival was similar in the 2 arms. Among patients who achieved hematologic CR, 3-year relapse-free survival was 91% with DAS and 88% with IM 400 mg. Grade 3 and 4 toxicities were most commonly hematologic, including thrombocytopenia in 18% and 8% of DAS and IM patients, respectively. DAS induced more complete cytogenetic response and deeper molecular responses after 12 months, compared with IM 400 mg, and with a median follow-up of 3.0 years there have been very few deaths, relapses, or progressions in the 2 arms. In summary, DAS compared with IM appeared to have more short-term cytogenetic and molecular response, more hematologic toxicity, and similar overall survival. This trial is registered at www.clinicaltrials.gov as NCT00070499.