SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+21 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Syndax Pharmaceuticals
Must not be taking: Strong CYP3A4 inducers
Disqualifiers: Acute promyelocytic leukemia, CNS leukemia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.
Will I have to stop taking my current medications?
The trial requires that you do not use certain medications, specifically strong CYP3A4 inducers or inhibitors, except for Itraconazole, Ketoconazole, Posaconazole, or Voriconazole. If you are taking any of these, you may need to stop or adjust them before participating.
How is the drug SNDX-5613 different from other treatments for acute myeloid leukemia?
SNDX-5613, also known as Revumenib or Revuforj, is unique because it targets specific genetic mutations in acute myeloid leukemia, offering a more personalized approach compared to traditional chemotherapy. This drug is part of a new wave of treatments focusing on the genetic and molecular aspects of the disease, which may improve outcomes for patients who do not respond well to standard therapies.
12345Eligibility Criteria
This trial is for adults with newly diagnosed acute myeloid leukemia (AML) who have specific genetic changes (KMT2A, NPM1, or NUP98 mutations) and can handle intensive chemotherapy. They should be in decent physical shape (ECOG ≤2), have good liver, kidney, and heart function, and not have been treated for AML before.Participant Groups
The study tests SNDX-5613 combined with a strong chemotherapy regimen called HiDAC to see how safe it is and how well it works against AML. Researchers will monitor participants' reactions to the treatment and check its effectiveness in patients with certain gene alterations.
1Treatment groups
Experimental Treatment
Group I: SNDX-5613Experimental Treatment3 Interventions
Dose Escalation:
* Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen.
* Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613.
* Maintenance Monotherapy: Cohorts will receive SNDX-5613.
Dose Expansion:
* Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen.
* Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC.
* Maintenance Monotherapy: Cohorts will receive SNDX-5613.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
The University of Texas, MD Anderson Cancer CenterHouston, TX
AdventHealth Blood & Marrow Transplant CenterOrlando, FL
Norton Cancer Institute, St. Matthews CampusLouisville, KY
More Trial Locations
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Who is running the clinical trial?
Syndax PharmaceuticalsLead Sponsor
References
WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. [2023]Intensive induction chemotherapy achieves complete remissions (CR) in >60% of patients with acute myeloid leukemia (AML) but overall survival (OS) is poor for relapsing patients not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be associated with substantial side effects, and less toxic strategies should be explored. Twenty AML patients in first CR (CR1) ineligible for allo-HSCT were treated with FDC101, an autologous RNA-loaded mature dendritic cell (mDC) vaccine expressing two leukemia-associated antigens (LAAs). Each dose consisted of 2.5-5 × 106 mDCs per antigen, given weekly until week 4, at week 6, and then monthly, during the 2-year study period. Patients were followed for safety and long-term survival. Treatment was well tolerated, with mild and transient injection site reactions. Eleven of 20 patients (55%) remained in CR, while 4 of 6 relapsing patients achieved CR2 after salvage therapy and underwent allo-HSCT. OS at five years was 75% (95% CI: 50-89), with 70% of patients ≥60 years of age being long-term survivors. Maintenance therapy with this DC vaccine was well tolerated in AML patients in CR1 and was accompanied by encouraging 5-year long-term survival.
Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. [2020]Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy. There is no standard of care for relapsed/refractory (R/R) AML, and no new therapies have shown consistently superior outcomes in this setting in over two decades. Vosaroxin is an anticancer quinolone derivative (AQD) that was evaluated in combination with cytarabine for the treatment of R/R AML in the randomized, double-blind, placebo-controlled, phase III VALOR study (n = 711). Compared with placebo/cytarabine, the vosaroxin/cytarabine regimen demonstrated favorable CR rates and survival in patients ⩾60 years of age, with toxicities similar to other AML regimens. Here we review outcomes of recent studies of commonly used chemotherapy regimens for the treatment of R/R AML and evaluate the results of the VALOR trial in the context of the current treatment landscape.
Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. [2020]The survival rate for acute myeloid leukemia remains unacceptably low, in large part owing to resistance to chemotherapy and high rates of relapse. There is an urgent need to develop new therapeutic modalities, in particular such that are tolerated by patients over the age of 60 years, who form the bulk of new acute myeloid leukemia diagnoses. Vosaroxin (SNS-595), a second-generation topoisomerase II inhibitor and DNA intercalating agent, shows promising preclinical and clinical activity against acute myeloid leukemia. Venetoclax (ABT-199), a selective Bcl-2 inhibitor, was recently approved for the treatment of acute myeloid leukemia.
Emerging therapies for acute myeloid leukemia. [2023]Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors. These agents are actively undergoing clinical investigation alone or in combination with available chemotherapy.
Treatment of Relapsed/Refractory Acute Myeloid Leukemia. [2022]Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled. These advances have paved the way for rational drug development as new "drugable" targets have emerged. Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration "breakthrough" designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat. In our practice, we treat most patients with relapsed/refractory AML on clinical trials, taking into consideration their prior treatment history and response to the same. We utilize targeted sequencing of genes frequently mutated in AML to identify "actionable" mutations, e.g., in FLT3 or IDH1/2, and incorporate small-molecule inhibitors of these oncogenic kinases into our therapeutic regimens whenever possible. In the absence of actionable mutations, we rationally combine conventional agents with other novel therapies such as monoclonal antibodies and other targeted drugs. For fit patients up to the age of 65, we often use high-dose cytarabine-containing backbone regimens. For older or unfit patients, we prefer hypomethylating agent-based therapy. Finally, all patients with relapsed/refractory AML are evaluated for allogeneic HSCT.