Combining SNDX-5613 with standard chemotherapy for newly diagnosed acute myeloid leukemia
Official title: A Phase 1b Study of Menin Inhibitor SNDX-5613 in Combination With Daunorubicin and Cytarabine in Newly Diagnosed Patients With Acute Myeloid Leukemia and NPM1 Mutated/FLT3 Wildtype or MLL/KMT2A Rearranged or NUP98 Alterations Disease
Run by National Cancer Institute (NCI) · NCT05886049 · Data updated 2026-11-12
This study is testing a new drug called SNDX-5613 combined with standard chemotherapy to see if it can improve treatment for people with newly diagnosed acute myeloid leukemia that has certain genetic mutations.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Enrollment | 38 (estimated) |
| Sponsor | National Cancer Institute (NCI) NIH |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 23 sites (Orange, California and 22 other locations) |
| Status | Recruiting |
| Started | June 20, 2024 |
| Main results expected | December 31, 2027 |
| Study ends | December 31, 2027 |
| Registry record updated | August 25, 2026 |
| Trial ID | NCT05886049 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are adults aged 18-75 with newly diagnosed AML featuring NPM1 mutations or MLL/KMT2A rearrangements who are eligible for intensive chemotherapy.
✕Probably not a fit
Patients under 18 years old or those with other types of AML not specified in the study may not benefit from this treatment.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase Ib trial evaluates the safety and optimal dosage of SNDX-5613 when used alongside standard chemotherapy treatments, daunorubicin and cytarabine, in patients with newly diagnosed acute myeloid leukemia (AML) that has specific genetic mutations. The study aims to determine the maximum tolerated dose and assess the drug's pharmacokinetics and potential interactions with other medications. By blocking survival signals in cancer cells, the combination treatment may enhance the effectiveness of chemotherapy, potentially leading to better patient outcomes.
Why it matters
Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with specific genetic mutations in AML.
How similar studies have gone: While this approach is novel in combining SNDX-5613 with standard chemotherapy for this specific patient population, similar studies have shown promise in targeting genetic mutations in cancer treatment.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Dose escalation: Patients ages 18-75 years at time of diagnosis with NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype with high-risk features (adverse risk genetics per European LeukemiaNet \[ELN\] 2022 criteria, age ≥ 60 years, or secondary AML defined as either arising from a prior hematological malignancy or therapy-related), MLL (KMT2A) rearranged or NUP98 altered, untreated AML and who are candidates for intensive induction chemotherapy. Patients with CD33+ AML are eligible for this protocol. * Dose expansion: Patients ages 18-75 years at time of diagnosis with NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype (any patient-does not require high-risk features), MLL (KMT2A) rearranged, or NUP98 altered, untreated AML and who are candidates for intensive induction chemotherapy. Patients with CD33+ AML are eligible for this protocol * Because no dosing or adverse event data are currently available on the use of SNDX-5613 in combination with daunorubicin and cytarabine in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%). Patients over the age of 65 must have an ECOG performance status of 0-1 * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except for patients with Gilbert's syndrome where required to be ≤ 3 x institutional ULN * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal (ULN) * Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 (via the Chronic Kidney Disease Epidemiology \[CKD-EPI\] glomerular filtration rate estimation) * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better * Ejection fraction \>= 50% (or \>= 45% if no evidence of congestive heart failure \[CHF\] or other cardiac symptoms) by transthoracic echocardiogram (TTE) or multi-gated acquisition (MUGA) scan * White blood cells (WBC) must be \< 25 x 10\^9/L. Hydroxyurea and leukapheresis are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped within 24 hours of initiation of protocol therapy. Must not have had any signs of leukostasis requiring cytoreduction * Female patients of childbearing potential must agree to use 2 forms of contraception from screening visit until 120 days following the last dose of study treatment. Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from screening visit until 180 days until the last dose of study treatment. They must also refrain from sperm donation from screening visit until 180 days following the last dose of study treatment * Patients must have previously untreated AML with no prior treatment other than hydroxyurea or intrathecal chemotherapy for central nervous system (CNS) prophylaxis/treatment. No chemotherapy for AML outside of hydroxyurea for treatment of leukostasis or all-trans retinoic acid (ATRA) for initially suspected acute promyelocytic leukemia (APL) (that is ruled out) is allowed * Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants Exclusion Criteria: * History of allergic reactions attributed to compounds of similar chemical or biologic composition to SNDX-5613, daunorubicin or cytarabine * Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous * Patient must not have received known strong or moderate CYP3A4 inhibitors, or strong CYP3A4 inducers (with the exception of antifungal prophylaxis with azoles) within 7 days of enrollment. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product * Pregnant women are excluded from this study because SNDX-5613 is a menin-KMT2A inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SNDX-5613, breastfeeding should be discontinued if the mother is treated with SNDX-5613. These potential risks may also apply to other agents used in this study * Isolated myeloid sarcoma (i.e., patients must have blood or marrow involvement with AML to enter the study) * Acute promyelocytic leukemia (French-American-British \[FAB\] M3) * Untreated, active central nervous system (CNS) involvement by AML. Patients are allowed to undergoing diagnostic lumbar puncture (LP) with intrathecal chemotherapy while on study * Uncontrolled symptomatic disseminated intravascular coagulopathy with active bleeding or signs of thrombosis * Patients with Fridericia's correction formula (QTcF) \>= 450 ms at screening; patients with right, left, or partial bundle branch blocks or a pacemaker who are asymptomatic are eligible regardless of QTC if cleared by cardiology for enrollment in the trial. Any factors that increase the risk of QTc prolongation or risk of arrhythmic event such as congenital long QT syndrome or family history of long QT syndrome * Patients who will exceed a lifetime anthracycline exposure of \> 550 mg/m\^2 daunorubicin or equivalent (or \> 400 mg/m\^2 daunorubicin or equivalent in the event of prior mediastinal radiation) if they receive the maximum potential exposure to anthracyclines per protocol (including both induction and reinduction cycles) * Patients with any gastrointestinal issue of the upper gastrointestinal (GI) tract that might affect oral drug absorption or ingestion (eg, gastric bypass, gastroparesis, etc) * Patients who have cirrhosis with a Child-Pugh score of B or C * Patients with Down Syndrome due to higher rates of chemotherapy-associated toxicities, and may have different pharmacokinetics, as well. Toxicities that occur at higher frequencies include cardiotoxicity, a known risk of SNDX-5613 treatment (i.e., QTcF prolongation) * Patients with myelodysplastic syndromes (MDS) treated with previous intensive induction regimens similar to 7+3
Where it's running
-
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States Recruiting -
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States Recruiting -
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States Recruiting
Show 17 more locations
-
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States Recruiting -
University of Kansas Clinical Research Center
Fairway, Kansas, United States Recruiting -
University of Kansas Cancer Center
Kansas City, Kansas, United States Recruiting -
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States Recruiting -
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States Recruiting -
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States Recruiting -
Dana-Farber Cancer Institute
Boston, Massachusetts, United States Recruiting -
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States Recruiting -
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States Recruiting -
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States Recruiting -
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States Recruiting -
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States Recruiting -
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States Recruiting -
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States Recruiting -
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States Recruiting -
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States Suspended -
University of Virginia Cancer Center
Charlottesville, Virginia, United States Active not recruiting
Study contacts
- Principal investigator: Alice S Mims — Ohio State University Comprehensive Cancer Center LAO
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
Decitabine plus FLAG‑Ida chemotherapy and total‑body irradiation before donor stem cell transplant for adults with high‑risk myeloid cancers
This test tries whether adding decitabine to FLAG‑Ida chemotherapy and total‑body irradiation before a donor stem cell transplant helps adults with high‑risk or relapsed myeloid blood cancers live longer and stay in remission.
-
Combination treatment for relapsed or refractory acute myeloid leukemia with specific mutations
This study is testing a new combination of two drugs for people with relapsed or hard-to-treat acute myeloid leukemia that has specific gene mutations to see if it helps them feel better.
-
CAR T Cell Therapy for Recurrent or Refractory Acute Myeloid Leukemia
This study is testing a new CAR T-cell therapy to see if it can help people with recurring or hard-to-treat acute myeloid leukemia by using modified immune cells to attack cancer cells.
-
Using edetate calcium disodium or succimer to treat acute myeloid leukemia or myelodysplastic syndrome during chemotherapy
This study is testing whether two drugs, edetate calcium disodium and succimer, can safely help people with acute myeloid leukemia or myelodysplastic syndrome feel better during chemotherapy.
-
Combining cladribine, idarubicin, cytarabine, and venetoclax for treating certain blood cancers
This study is testing a new combination of four medications to see if it helps people with certain types of blood cancers feel better and live longer.
-
Tailored exercise program to improve quality of life for adults with hematologic cancers
This pilot trial tests a personalized 16-week exercise program to see if it’s feasible and helpful for adults with acute myeloid leukemia, lymphoma, or multiple myeloma after first-line treatment.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.