SNDX-5613 + Chemotherapy for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
+16 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: National Cancer Institute (NCI)
Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers
Disqualifiers: Pregnancy, CNS involvement, Down syndrome, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This phase Ib trial tests the safety, side effects, and best dose of SNDX-5613 when given in combination with the standard chemotherapy treatment (daunorubicin and cytarabine) in treating patients with newly diagnosed acute myeloid leukemia that has changes in the NPM1 gene or MLL/KMT2A gene. SNDX-5613 blocks signals passed from one molecule to another inside cancer cells that are needed for cancer cell survival. Drugs used in chemotherapy, such as daunorubicin and cytarabine, 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. Adding SNDX-5613 to the standard chemotherapy treatment may be able to shrink or stabilize the cancer for longer than the standard chemotherapy treatment alone.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but you cannot have received strong or moderate CYP3A4 inhibitors or inducers within 7 days of enrollment. It's important to discuss your current medications with the trial team to ensure there are no interactions.
How is the drug SNDX-5613 (Revumenib, Revuforj) different from other treatments for acute myeloid leukemia?
SNDX-5613 (Revumenib, Revuforj) is unique because it targets specific genetic mutations in acute myeloid leukemia, offering a more personalized approach compared to traditional chemotherapy, which often has high relapse rates and is less effective in older patients.
12345Eligibility Criteria
This trial is for adults aged 18-75 with newly diagnosed acute myeloid leukemia that has specific gene changes (NPM1 or MLL/KMT2A) and are fit for intensive chemotherapy. Participants must have good organ function, an ECOG performance status of <=2, and if HIV-positive, they need undetectable viral load on effective therapy. Those with chronic hepatitis B or C must be on suppressive therapy or cured.Inclusion Criteria
I agree to use birth control during the study.
Specific laboratory values within defined ranges (e.g., total bilirubin, AST/ALT, GFR)
My heart functions within specific health parameters.
+8 more
Exclusion Criteria
Patients with Down Syndrome
History of allergic reactions to specific compounds
Pregnant or breastfeeding women
+10 more
Participant Groups
The trial is testing the safety and optimal dose of SNDX-5613 added to standard chemo drugs Daunorubicin and Cytarabine in patients with certain genetic types of acute myeloid leukemia. The goal is to see if this new combination can better shrink or control cancer compared to standard treatment alone.
1Treatment groups
Experimental Treatment
Group I: Treatment (revumenib, daunorubicin, cytarabine)Experimental Treatment8 Interventions
See Detailed Description.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Chicago Comprehensive Cancer CenterChicago, IL
Carolinas Medical Center/Levine Cancer InstituteCharlotte, NC
Wake Forest University Health SciencesWinston-Salem, NC
UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, CA
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead 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.
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.
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.
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.
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.