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
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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 75 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 2 years
- Procedures mentioned: Infusions, Biopsies
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "INDUCTION: Patients receive revumenib orally (PO) every 12 hours (Q12h) on days 2-28, daunorubicin intravenously (IV) over 15 to 30 minutes on days 1-3, and cytarabine by continuous IV infusion (CIV) on days 1-7 in the absence of disease progression or unacceptable toxicity."
- "Patients also undergo a transthoracic echocardiogram (ECHO) or multigated acquisition scan (MUGA) during screening, bone marrow aspiration and biopsy during screening and at the end of Induction, and collection of blood during screening, on days 2, 3, 15, and at the end of Induction."
- "Patients also undergo a transthoracic ECHO or MUGA on day 1 and bone marrow aspiration and biopsy at the end of Re-Induction."
- "Patients also undergo bone marrow aspiration and biopsy at the end of Consolidation, and collection of blood on days 2, 3, 15, and at the end of Consolidation."
- "After completion of study treatment, patients are followed for up to 2 years or until death or relapse, whichever occurs first."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests the safety, side effects, and best dose of SNDX-5613 with two standard chemotherapy drugs, daunorubicin and cytarabine. It is for adults ages 18–75 with newly diagnosed acute myeloid leukemia (AML), a blood cancer, with certain changes in the NPM1, MLL/KMT2A, or NUP98 genes.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be ages 18–75 with untreated AML and able to receive strong chemotherapy. Only certain earlier treatments are allowed.
- Have an MLL/KMT2A or NUP98 gene change, or an NPM1 change without FLT3-ITD or FLT3-TKD changes. In the dose-finding part, people with NPM1 changes must also have higher-risk disease.
- Be able to care for yourself and be out of bed for at least half the day. People over 65 must be fully active or limited only in hard physical activity.
- Meet the study’s liver, kidney, and heart test limits.
- Have a white blood cell count below the study limit. Treatment to lower it is allowed, but signs of blocked blood flow from leukemia cells may rule you out.
- If you have HIV or hepatitis B or C, meet the study’s treatment and virus-control rules. Other cancers are allowed if they will not affect this study’s safety or results.
- Follow the study’s birth control rules. Women who can become pregnant must use two methods through 120 days after treatment. Men must follow pregnancy-prevention and sperm-donation rules through 180 days after treatment.
- Be able to understand and sign a consent form, or have a legally authorized person give consent for you.
Who can't join
- Allergy to drugs like the study drugs, or an uncontrolled illness that makes treatment unsafe.
- Pregnancy. Breastfeeding must stop during treatment.
- Certain medicines that affect how the body breaks down drugs within 7 days before joining. Some antifungal medicines are allowed.
- Acute promyelocytic leukemia, AML only in a tumor outside the blood or bone marrow, or untreated active AML in the brain or spinal cord.
- An uncontrolled blood-clotting problem with bleeding or clots, or certain heart rhythm problems or risks. Some people with a pacemaker or other electrical heart changes may join with a heart doctor’s approval.
- Prior chemotherapy that would put you above the lifetime limit for certain drugs, or prior strong chemotherapy for myelodysplastic syndromes, a group of bone marrow diseases.
- Stomach or upper gut problems that affect swallowing or absorbing the study drug, or moderate to severe liver scarring.
- Down syndrome.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility 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
Study sites (23)
CA
- UC Irvine Health/Chao Family Comprehensive Cancer Center · Orange, CA 92868Site Public Contact · Study contact · 877-827-8839 · ucstudy@uci.eduKiran Naqvi · Principal investigatorMore trials in Orange
- University of California Davis Comprehensive Cancer Center · Sacramento, CA 95817More trials in Sacramento
FL
- UM Sylvester Comprehensive Cancer Center at Aventura · Aventura, FL 33180Site Public Contact · Study contact · 954-461-2180Sangeetha Venugopal · Principal investigatorMore trials in Aventura
- UM Sylvester Comprehensive Cancer Center at Coral Gables · Coral Gables, FL 33146Site Public Contact · Study contact · 305-243-2647Sangeetha Venugopal · Principal investigatorMore trials in Coral Gables
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach · Deerfield Beach, FL 33442Site Public Contact · Study contact · 305-243-2647Sangeetha Venugopal · Principal investigatorMore trials in Deerfield Beach
- University of Miami Miller School of Medicine-Sylvester Cancer Center · Miami, FL 33136Site Public Contact · Study contact · 305-243-2647Sangeetha Venugopal · Principal investigatorMore trials in Miami
- UM Sylvester Comprehensive Cancer Center at Plantation · Plantation, FL 33324Site Public Contact · Study contact · 305-243-2647Sangeetha Venugopal · Principal investigatorMore trials in Plantation
IL
- University of Chicago Comprehensive Cancer Center · Chicago, IL 60637Site Public Contact · Study contact · 773-702-8222 · cancerclinicaltrials@bsd.uchicago.eduOlatoyosi M. Odenike · Principal investigatorMore trials in Chicago
KS
- University of Kansas Clinical Research Center · Fairway, KS 66205Site Public Contact · Study contact · 913-588-3671 · KUCC_Navigation@kumc.eduJesus Gonzalez Lugo · Principal investigatorMore trials in Fairway
- University of Kansas Cancer Center · Kansas City, KS 66160Site Public Contact · Study contact · 913-588-3671 · KUCC_Navigation@kumc.eduJesus Gonzalez Lugo · Principal investigatorMore trials in Kansas City
- University of Kansas Hospital-Indian Creek Campus · Overland Park, KS 66211Site Public Contact · Study contact · 913-588-3671 · KUCC_Navigation@kumc.eduJesus Gonzalez Lugo · Principal investigatorMore trials in Overland Park
- University of Kansas Hospital-Westwood Cancer Center · Westwood, KS 66205Site Public Contact · Study contact · 913-588-3671 · KUCC_Navigation@kumc.eduJesus Gonzalez Lugo · Principal investigatorMore trials in Westwood
MA
- Dana-Farber Cancer Institute · Boston, MA 02215Site Public Contact · Study contact · 877-442-3324Richard M. Stone · Principal investigatorMore trials in Boston
MD
- University of Maryland/Greenebaum Cancer Center · Baltimore, MD 21201Site Public Contact · Study contact · 800-888-8823Vu H. Duong · Principal investigatorMore trials in Baltimore
NC
- UNC Lineberger Comprehensive Cancer Center · Chapel Hill, NC 27599Site Public Contact · Study contact · 877-668-0683 · cancerclinicaltrials@med.unc.eduJoshua F. Zeidner · Principal investigatorMore trials in Chapel Hill
- Carolinas Medical Center/Levine Cancer Institute · Charlotte, NC 28203Site Public Contact · Study contact · 800-804-9376Brittany K. Ragon · Principal investigatorMore trials in Charlotte
- Wake Forest University Health Sciences · Winston-Salem, NC 27157Site Public Contact · Study contact · 336-713-6771Matthew J. Wieduwilt · Principal investigatorMore trials in Winston-Salem
OH
- University of Cincinnati Cancer Center-UC Medical Center · Cincinnati, OH 45219Site Public Contact · Study contact · 513-584-7698 · cancer@uchealth.comEmily K. Curran · Principal investigatorMore trials in Cincinnati
- Ohio State University Comprehensive Cancer Center · Columbus, OH 43210Site Public Contact · Study contact · 800-293-5066 · Jamesline@osumc.eduAlice S. Mims · Principal investigatorMore trials in Columbus
- University of Cincinnati Cancer Center-West Chester · West Chester, OH 45069Site Public Contact · Study contact · 513-584-7698 · cancer@uchealth.comEmily K. Curran · Principal investigatorMore trials in West Chester
OK
- University of Oklahoma Health Sciences Center · Oklahoma City, OK 73104Site Public Contact · Study contact · 405-271-8777 · ou-clinical-trials@ouhsc.eduMohamad Khawandanah · Principal investigatorMore trials in Oklahoma City
UT
- Huntsman Cancer Institute/University of Utah · Salt Lake City, UT 84112Site Public Contact · Study contact · 888-424-2100 · cancerinfo@hci.utah.eduPaul J. Shami · Principal investigatorMore trials in Salt Lake City
VA
- University of Virginia Cancer Center · Charlottesville, VA 22908More trials in Charlottesville