A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1)
A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia and Other Selected Hematologic Malignancies, With and Without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation (Horizen-1)
1 other identifier
interventional
606
12 countries
104
Brief Summary
A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2022
Longer than P75 for phase_1
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 26, 2021
CompletedFirst Posted
Study publicly available on registry
August 3, 2021
CompletedStudy Start
First participant enrolled
February 28, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
March 24, 2026
March 1, 2026
5.3 years
July 26, 2021
March 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Number of patients with adverse events and serious adverse events in Phase 1
Assessment of safety of DSP-5336 administered in participants with advanced hematologic malignancies by reporting of adverse events and serious adverse events in Phase 1
30 days from last dose
Determination of Recommended Phase 2 Dose (RP2D)
The RP2D is based on adverse events, pharmacokinetics, and clinical response
Within 4 months from first dose
Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the combination venetoclax and azacitidine arm
The RP2D is based on adverse events, pharmacokinetics, and clinical response
Within 4 months from first dose
Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the gilteritinib arm
The RP2D is based on assessment of Dose Limiting Toxicities
Within 4 months from first dose
Optimal dose of DSP-5336 (RP2D) for patients newly diagnosed with AML enrolled into the combination venetoclax and azacitidine arm
The RP2D is based on adverse events, pharmacokinetics and clinical response
Within 4 months from the first dose
Determination of Recommended Phase 2 Dose (RP2D) for patients enrolled into the 7 + 3 arm
The RP2D is based on assessment of Dose Limiting Toxicities
Within 4 months from first dose
Number of patients achieving complete response (CR) and complete response with partial hematologic recovery (CRh) in Phase 2
Disease response defined by the FDA guidance and ELN2017
Approximately 6 months after first dose
Secondary Outcomes (13)
The maximum observed concentration (Cmax) of of DSP-5336, venetoclax and gilteritinib
Approximately 3 months after first dose
Area under the plasma concentration vs. time curve (AUClast) of DSP-5336, venetoclax and gilteritinib
Approximately 3 months after first dose
T(1/2) of DSP-5336, venetoclax and gilteritinib
Approximately 3 months after first dose
The maximum observed concentration (Cmax) of of DSP-5336 in the presence of high-fat meal
Approximately 3 months after first dose
Area under the plasma concentration vs. time curve (AUClast) of DSP-5336 in the presence of high-fat meal
Approximately 3 months after first dose
- +8 more secondary outcomes
Study Arms (14)
Phase 1 - Arm A
EXPERIMENTALR/R acute leukemia without CYP3A4 inhibitor azoles
Phase 1 - Arm B
EXPERIMENTALR/R acute leukemia with CYP3A4 inhibitor azoles
Phase 1 - Arm C
EXPERIMENTALHigh-risk MDS after HMA
Phase 1 - Arm D
EXPERIMENTALPatients with refractory MM
Phase 1 - Arm E
EXPERIMENTALR/R AML with NPM1m or KMT2Ar
Phase 1 - Arm F
EXPERIMENTALR/R AML with FLT3m + NPM1m or KMT2Ar
Phase 2 - Arm G
EXPERIMENTALR/R AML with MLLr
Phase 2 - Arm H
EXPERIMENTALR/R AML with NPM1m
Phase 2 - Arm I
EXPERIMENTALR/R ALL with MLLr
Phase 2 - Arm J
EXPERIMENTALR/R acute leukemia with MLLr
Phase 2 - Arm K
EXPERIMENTALR/R AML with NPM1m
Phase 1 - Arm L
EXPERIMENTALNewly diagnosed AML KMT2Ar FIT or UNFIT
Phase 1 - Arm M
EXPERIMENTALNewly diagnosed AML NPM1m UNFIT only
Phase 1 - Arm N
EXPERIMENTALNewly diagnosed AML with KMT2Ar or NPM1m
Interventions
DSP-5336 orally
Posaconazole, Voriconazole, or Fluconazole
Eligibility Criteria
You may qualify if:
- For patients in Phase I:
- Have a diagnosis of relapsed or refractory AML, ALL or acute leukemia of ambiguous lineage according to World Health Organization (WHO) 2022 classification, or, in selected sites and regions, a diagnosis of MDS or MM as determined by pathology review at the treating institution, and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage or, in selected sites and regions, for MM or MDS. If acute leukemia patients are transformation from MDS or other hematologic malignancies, patients need to receive available standard therapies as acute leukemia after AML transformation and before enrolling this trial. In regions or countries where required by regulatory authorities, participants must have a documented KMT2A (MLL) fusion or NPM1 mutation, including those with coexisting FLT3 genomic alterations and/or IDH1/2 mutation. Participants who are candidates for stem cell transplantation must have been offered this therapeutic option.
- For patients with MDS (selected sites and regions):
- Patients with MDS must have bone marrow blasts ≥ 5%
- Patients with MDS must have relapsed or refractory disease and have exhausted available standard therapies including at least 2 cycles of treatment with HMA
- For patients with MM (selected sites and regions):
- Have a confirmed diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) 2016 classification (Kumar, 2016) and whose disease has progressed after treatment with a minimum of 3 prior anti-myeloma regimens including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb); patients must not be candidates for available therapies with established clinical benefit
- Have measurable disease as defined in the protocol
- Meet the laboratory parameters set in the protocol
- For patients with relapsed/refractory AML in the venetoclax and azacitidine combination cohort (in countries and sites where permitted):
- Have MLLr or NPM1m.
- For patients with relapsed/refractory AML in the gilteritinib combination cohort (in countries and sites where permitted):
- Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
- For patients with relapsed/refractory AML with NPM1 enrolled in the RP2D confirmation cohort:
- Must have ≥5% blasts in bone marrow by morphologic assessment
- +21 more criteria
You may not qualify if:
- Has a left ventricular ejection fraction (LVEF) \<50%, as determined by ECHO
- Histological diagnosis of acute promyelocytic leukemia
- Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336
- Have abnormal ECGs at screening that are clinically significant, such as (QTc \>480 msec, with QTc corrected according to Fridericia's formula (QTcF). For clinical sites in the UK, have abnormal ECGs at screening that are clinically significant, such as QTc ≥470 msec and ≥450 msec with QTc corrected according to Fridericia's formula (QTcF), for females and males, respectively. In addition, patients with a history of prolonged QT syndrome or who are required to take therapies associated with QT-interval prolongation are excluded.
- Note: In case of bundle branch block, QT interval correction can be performed.
- Has an active and uncontrolled, bacterial, viral, or fungal infection requiring parenteral therapy. Note: Patients must be afebrile with negative blood cultures at least 72 hours prior to Cycle 1 Day 1.
- Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole, isavuconazole and itraconazole. Other antifungals that are used as standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor.
- Had major surgery within 28 days prior to the first dose of DSP-5336
- Has active central nervous system leukemia (prophylactic intrathecal chemotherapy is allowed).
- Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336. For clinical sites in the UK, underwent CAR-T therapy or other modified T-cell therapy within 6 months prior to the first dose of DSP-5336.
- Received a donor lymphocyte infusion within 28 days prior to the first dose of DSP-5336, or receiving immunosuppressive therapy post-HSCT at the time of screening, or with clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD
- Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) or other investigational treatment within 7 days or 5 half-lives, whichever is shortest, prior to the first dose of DSP-5336
- In the opinion of the treating investigator, have any concurrent conditions that could pose an undue medical hazard or interfere with interpretation of study results; these conditions include, but are not limited to: clinically significant non-healing or healing wounds; concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV; see Section 21.2); concurrent unstable angina; concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation); recent (within the prior 6 months) myocardial infarction; acute coronary syndrome within the previous 6 months; significant pulmonary disease (shortness of breath at rest or on mild exertion), eg, due to concurrent severe obstructive pulmonary disease, concurrent hypertension not controlled with concomitant medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 6 months
- Have a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of hepatitis B surface antigen, all being indicative of active infection.
- For sites in Japan, Taiwan, and Korea only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs) antibody test should be performed if HBsAg is negative. If HBc antibody or HBs antibody test is positive, HBV DNA quantification test should be performed to confirm that HBV DNA is negative.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (104)
Hoag Family Cancer Center
Newport Beach, California, 92663, United States
Stanford University
Palo Alto, California, 94304, United States
Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007, United States
University of Miami
Miami, Florida, 33136, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Northwestern
Chicago, Illinois, 60611, United States
Sibley Memorial Hospital
Baltimore, Maryland, 20016, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Johns Hopkins Main Center
Baltimore, Maryland, 21287, United States
Tufts University
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Atlantic Health
Morristown, New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Columbia University
New York, New York, 10032, United States
UNC Hospital
Chapel Hill, North Carolina, 27514, United States
Duke University
Durham, North Carolina, 27705, United States
Atrium Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oncology Associates of Oregon
Eugene, Oregon, 97401, United States
Sidney Kimmel Comprehensive Cancer Center
Philadelphia, Pennsylvania, 19107, United States
Allegheny Health Network
Pittsburgh, Pennsylvania, 15224, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
TriStar Centennial Medical Center
Nashville, Tennessee, 37203, United States
MDACC
Houston, Texas, 77030, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Intermountain Healthcare
Salt Lake City, Utah, 84143, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Virginia Oncology Associates
Norfolk, Virginia, 23502, United States
ZNA Cadix
Antwerp, Belgium
UZ Ghent
Ghent, 9000, Belgium
University Hospitals Leuven
Leuven, Belgium
AZ Delta
Roeselare, Belgium
Tom Baker Cancer Center
Calgary, Alberta, T2N 5G2, Canada
University of Alberta
Edmonton, T6G 2R3, Canada
Centre Hospitalier Universitaire d'Angers
Angers, France
Hopital Avicenne
Bobigny, 93000, France
Centre Hospitalier Le Mans
Le Mans, France
Hopital Claude Huriez
Lille, 59037, France
Centre Hospitalier Universitaire de Limoges
Limoges, France
Hospices Civils de Lyon
Lyon, France
Institut Paoli-Calmettes
Marseille, France
CHU de Nantes
Nantes, 44093, France
CHU de Nice - Hôpital l'Archet 1
Nice, France
Hopital Saint-Louis
Paris, France
CHU Bordeaux
Talence, 33000, France
Institut Gustave Roussy
Villejuif, 94800, France
IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Policlinico Sant'Orsola
Bologna, Italy
Ospedale di Busto Arsizio
Busto Arsizio, 21052, Italy
Ospedale Policlinico San Martino, IRCCS
Genoa, Italy
IRCCS istituto Romagnolo per lo studio dei tumori "Dino Amadori"
Meldola, Italy
Istituto Oncologico Veneto (IOV), IRCCS
Padua, Italy
Università degli Studi di Perugia
Perugia, Italy
Azienda USL della Romagna, Ospedale Santa Maria delle Croci di Ravenna
Ravenna, 48121, Italy
PU A. Gemelli, Università Cattolica del Sacro Cuore
Rome, Italy
Universita' Degli Studi Di Torino
Turin, Italy
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577, Japan
University of Fukui Hospital
Yoshida-gun, Fukui, 910-1193, Japan
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1295, Japan
Tokai University Hospital
Isehara-shi, Kanagawa, 259-1193, Japan
Nagasaki University Hospital
Nagasaki, Nagasaki, 852-8501, Japan
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, 113-8603, Japan
Tokyo Metropolitan Komagome Hospital
Bunkyō City, 113-8677, Japan
Kyushu University Hospital
Fukuoka, 812-8582, Japan
Hokkaido University Hospital
Hokkaido, 060-8648, Japan
Tohoku University Hospital
Miyagi, 980-8574, Japan
Okayama University Hospital
Okayama, 700-8558, Japan
Osaka University Hospital
Osaka, 565-0871, Japan
National University Cancer Institute
Singapore, 119074, Singapore
Chonnam National University Hwasun Hospital
Hwasun, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
The Catholic University of Korea
Seoul, South Korea
Hospital General Universitario De Albacete
Albacete, Spain
Hospital Universitari Vall D'Hebron
Barcelona, Spain
Institut Catala d'Oncologia
Barcelona, Spain
Hospital San Pedro de Alcantara
Cáceres, Spain
Hospital Universitario De Gran Canaria Dr. Negrin
Las Palmas, Spain
MD Anderson Cancer Center
Madrid, Spain
Hospital Universitario Central De Asturias
Oviedo, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Fundacion Instituto de Investigacion Marques de Valdecilla
Santander, Spain
Complexo Hospitalario Universitario De Santiago
Santiago de Compostela, Spain
Hospital Universitario y Politecnico La Fe
Valencia, Spain
University Hospital Basel
Basel, 4031, Switzerland
University Hospital Bern Inselspital
Bern, 3010, Switzerland
Universitaetsspital Zuerich - Haematology
Zurich, 8091, Switzerland
Taichung Veterans General Hospital
Taichung, Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
University Hospitals of Birmingham Centre for Clinical Hematology
Birmingham, United Kingdom
Bristol Hematology & Oncology Centre
Bristol, United Kingdom
NHS Lothian Western General
Edinburgh, EH4 2XU, United Kingdom
King's College Hospital
London, United Kingdom
Sarah Cannon Research Institute
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Christie Hospital NHS Foundation Trust
Manchester, United Kingdom
Churchill Hospital Oxford
Oxford, United Kingdom
University Hospitals of North Midlands NHS Foundation Trust
Stoke-on-Trent, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2021
First Posted
August 3, 2021
Study Start
February 28, 2022
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
March 24, 2026
Record last verified: 2026-03