Trial Title:
Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene
NCT ID:
NCT05886049
Condition:
Acute Myeloid Leukemia With KMT2A Rearrangement
Acute Myeloid Leukemia With NPM1 Mutation
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Daunorubicin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IV
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
.beta.-Cytosine arabinoside
Other name:
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-.beta.-D-Arabinofuranosylcytosine
Other name:
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-Beta-D-arabinofuranosylcytosine
Other name:
1.beta.-D-Arabinofuranosylcytosine
Other name:
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
Other name:
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Other name:
Alexan
Other name:
Ara-C
Other name:
ARA-cell
Other name:
Arabine
Other name:
Arabinofuranosylcytosine
Other name:
Arabinosylcytosine
Other name:
Aracytidine
Other name:
Aracytin
Other name:
Aracytine
Other name:
Beta-Cytosine Arabinoside
Other name:
CHX-3311
Other name:
Cytarabinum
Other name:
Cytarbel
Other name:
Cytosar
Other name:
Cytosine Arabinoside
Other name:
Cytosine-.beta.-arabinoside
Other name:
Cytosine-beta-arabinoside
Other name:
Erpalfa
Other name:
Starasid
Other name:
Tarabine PFS
Other name:
U 19920
Other name:
U-19920
Other name:
Udicil
Other name:
WR-28453
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Given IV
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
Daunomycin
Other name:
Daunorrubicina
Other name:
DNR
Other name:
Leukaemomycin C
Other name:
Rubidomycin
Other name:
Rubomycin C
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNV Scan
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Revumenib
Description:
Given PO
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613
Other name:
Menin-MLL Inhibitor SNDX-5613
Other name:
Menin-MLL Interaction Inhibitor SNDX-5613
Other name:
SNDX 5613
Other name:
SNDX-5613
Other name:
SNDX5613
Intervention type:
Procedure
Intervention name:
Transthoracic Echocardiography
Description:
Undergo transthoracic ECHO
Arm group label:
Treatment (revumenib, daunorubicin, cytarabine)
Other name:
TTE
Summary:
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.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and
safety of revumenib (SNDX-5613) combined with 7 + 3 induction in newly diagnosed,
untreated, NPM1-mutated/FLT3-ITD wild type and NPM1-mutated/FLT3-TKD wild type or
MLL(KMT2A)-rearranged, acute myeloid leukemia (AML) patients >= 18-75 years old who are
candidates for intensive induction therapy.
II. To determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and
safety of SNDX-5613 combined with one cycle of consolidation with high dose cytarabine in
newly diagnosed AML patients in complete response/complete response with incomplete count
recovery (CR/Cri) after intensive induction therapy with 7+3 for NPM1-mutated/FLT3-ITD
wild type and NPM1-mutated/FLT3-TKD wild type or MLL (KMT2A)-rearranged AML patients >=
18-75 years old who are candidates for intensive therapy.
SECONDARY OBJECTIVES:
I. Evaluate the pharmacokinetics of SNDX-5613 with this combination regimen and
characterize clinically relevant drug-drug interactions with antifungal agents.
II. To determine the number of patients with CR/CRi out of the total number of patients
treated at each dose level of this regimen.
EXPLORATORY OBJECTIVES:
I. Explore potential biomarker indicators of response and resistance in AML samples.
II. To determine the measurable residual disease negative (MRD) response (CR/Cri) and its
relation to CR/Cri status out of the total number of patients treated at each dose level
of this regimen.
III. Determine number of patients that undergo hematopoietic stem cell transplant (HSCT)
out of the total number of patients treated at each dose level of this regimen.
IV. Assess changes in OATP1B and CYP3A plasma biomarkers during treatment with SNDX-5613
with or without antifungal agents.
V. Determine duration of response.
OUTLINE: This is a phase Ib, dose-escalation study of revumenib followed by a
dose-expansion study.
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 who achieve a response to Induction treatment continue to
Consolidation treatment. Patients with persistent disease continue to Re-Induction
treatment. 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.
RE-INDUCTION: Patients receive revumenib PO Q12h on days 2-28, daunorubicin IV over 15 to
30 minutes on days 1-2, and cytarabine CIV on days 1-5 in the absence of disease
progression or unacceptable toxicity. Patients who achieve a response to Re-Induction
treatment continue to Consolidation. Patients also undergo a transthoracic ECHO or MUGA
on day 1 and bone marrow aspiration and biopsy at the end of Re-Induction.
CONSOLIDATION: Patients receive revumenib PO Q12h on days 2-28 and cytarabine CIV on days
1-3 in the absence of disease progression or unacceptable toxicity. 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 30 days or until death,
whichever occurs first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Induction therapy: Patients ages 18-75 years at time of diagnosis with
NPM1-mutated/FLT3-ITD wildtype and NPM1-mutated/FLT3-TKD wildtype or MLL (KMT2A)
rearranged untreated AML and who are candidates for intensive induction chemotherapy
- 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%)
- Total bilirubin =< 2 x institutional upper limit of normal (ULN), except for
patients with Gilbert's syndrome
- 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 120 days until the last dose
of study treatment. They must also refrain from sperm donation from screening visit
until 120 days following the last dose of study treatment
- Patients must have previously untreated AML with no prior treatment other than
hydroxyurea. 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 that would make participation in
this study unduly burdensome or unsafe for patient
- Patient must not have received known strong or moderate CYP3A4 inhibitors, or strong
CYP3A4 inducers (with the exception of the antifungal) or sensitive/narrow
therapeutic substrates of MATE1 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)
- Active central nervous system (CNS) involvement by AML
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Kiran Naqvi
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Aventura
Address:
City:
Aventura
Zip:
33180
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
954-461-2180
Investigator:
Last name:
Sangeetha Venugopal
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Coral Gables
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Sangeetha Venugopal
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Sangeetha Venugopal
Email:
Principal Investigator
Facility:
Name:
University of Miami Miller School of Medicine-Sylvester Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Sangeetha Venugopal
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Plantation
Address:
City:
Plantation
Zip:
33324
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Sangeetha Venugopal
Email:
Principal Investigator
Facility:
Name:
University of Chicago Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
773-702-8222
Email:
cancerclinicaltrials@bsd.uchicago.edu
Investigator:
Last name:
Olatoyosi M. Odenike
Email:
Principal Investigator
Facility:
Name:
Carolinas Medical Center/Levine Cancer Institute
Address:
City:
Charlotte
Zip:
28203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-804-9376
Investigator:
Last name:
Brittany K. Ragon
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-UC Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Emily K. Curran
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Alice S. Mims
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-West Chester
Address:
City:
West Chester
Zip:
45069
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Emily K. Curran
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Mohamad Khawandanah
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
434-243-6303
Email:
uvacancertrials@hscmail.mcc.virginia.edu
Investigator:
Last name:
Daniel R. Reed
Email:
Principal Investigator
Start date:
June 20, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05886049
