A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1)

March 20, 2026 updated by: Sumitomo Pharma America, Inc.

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)

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

DSP-5336-101 is a phase 1/2 open-label, dose escalation, dose expansion study in which the safety, PK, pharmacodynamics, and clinical activity of orally administered DSP-5336 will be evaluated in patients with relapsed or refractory AML, ALL, or acute leukemia of ambiguous lineage, and in selected sites and regions, in adult patients with high-risk relapsed or refractory MDS or relapsed MM.

Additionally, the safety and clinical activity of orally administered DSP-5336 will be evaluated in combination with Standard-of-Care (SOC) AML treatments including: (a) the SOC nonintensive regimen (venetoclax + azacitidine) or (b) the SOC intensive regimen (cytarabine + daunorubicin induction, 7+3) in patients with newly diagnosed AML who have MLLr or NPM1m.

Study Type

Interventional

Enrollment (Estimated)

606

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Antwerp, Belgium
      • Ghent, Belgium, 9000
        • Recruiting
        • UZ Ghent
        • Principal Investigator:
          • Ine Moors, MD
        • Contact:
      • Leuven, Belgium
        • Recruiting
        • University Hospitals Leuven
        • Principal Investigator:
          • Johan Maertens, MD
        • Contact:
      • Roeselare, Belgium
        • Recruiting
        • AZ Delta
        • Contact:
        • Principal Investigator:
          • Dries Deeren, MD
  • Canada
      • Edmonton, Canada, T6G 2R3
        • Recruiting
        • University of Alberta
        • Contact:
        • Principal Investigator:
          • Joseph Brandwein, MD
    • Alberta
  • France
      • Angers, France
        • Recruiting
        • Centre Hospitalier Universitaire d'Angers
        • Principal Investigator:
          • Corentin Orvain, MD
        • Contact:
      • Bobigny, France, 93000
      • Le Mans, France
      • Lille, France, 59037
      • Limoges, France
      • Lyon, France
      • Marseille, France
        • Recruiting
        • Institut Paoli-Calmettes
        • Contact:
        • Principal Investigator:
          • Sylvain Garciaz, MD
      • Nantes, France, 44093
      • Nice, France
        • Recruiting
        • Chu de Nice - Hôpital L'Archet 1
        • Principal Investigator:
          • Thomas Cluzeau, MD
        • Contact:
      • Paris, France
        • Recruiting
        • Hôpital Saint-Louis
        • Contact:
        • Principal Investigator:
          • Emmanuel Raffoux, MD
      • Talence, France, 33000
      • Villejuif, France, 94800
  • Italy
      • Bologna, Italy
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Policlinico Sant'Orsola
        • Contact:
          • Cristina Papayannidis, MD
        • Principal Investigator:
          • Cristina Papayannidis, MD
      • Busto Arsizio, Italy, 21052
      • Genoa, Italy
      • Meldola, Italy
        • Recruiting
        • IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"
        • Contact:
      • Padua, Italy
        • Not yet recruiting
        • Istituto Oncologico Veneto (IOV), IRCCS
        • Contact:
      • Perugia, Italy
      • Ravenna, Italy, 48121
        • Not yet recruiting
        • Azienda USL della Romagna, Ospedale Santa Maria delle Croci di Ravenna
        • Contact:
      • Rome, Italy
      • Turin, Italy
  • Japan
      • Bunkyō City, Japan, 113-8677
        • Not yet recruiting
        • Tokyo Metropolitan Komagome Hospital
        • Contact:
      • Fukuoka, Japan, 812-8582
        • Recruiting
        • Kyushu University Hospital
        • Contact:
        • Principal Investigator:
          • Takahiro Shima, MD
      • Hokkaido, Japan, 060-8648
        • Not yet recruiting
        • Hokkaido University Hospital
        • Contact:
        • Principal Investigator:
          • Takanori Teshima, MD
      • Miyagi, Japan, 980-8574
        • Recruiting
        • Tohoku University Hospital
        • Principal Investigator:
          • Hisayuki Yokoyama, MD
        • Contact:
      • Okayama, Japan, 700-8558
        • Recruiting
        • Okayama University Hospital
        • Contact:
        • Principal Investigator:
          • Noboru Asada, MD
      • Osaka, Japan, 565-0871
        • Recruiting
        • Osaka University Hospital
        • Contact:
        • Principal Investigator:
          • Kentaro Fukushima, MD
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
        • Principal Investigator:
          • Junichiro Yuda, MD
    • Fukui
      • Yoshida-gun, Fukui, Japan, 910-1193
        • Recruiting
        • University of Fukui Hospital
        • Contact:
        • Principal Investigator:
          • Naoko Hosono, MD
    • Fukushima
      • Fukushima, Fukushima, Japan, 960-1295
        • Recruiting
        • Fukushima Medical University Hospital
        • Contact:
        • Principal Investigator:
          • Takayuki Ikezoe, MD
    • Kanagawa
      • Isehara-shi, Kanagawa, Japan, 259-1193
        • Recruiting
        • Tokai University Hospital
        • Contact:
        • Principal Investigator:
          • Yoshiaki Ogawa, MD
    • Nagasaki
      • Nagasaki, Nagasaki, Japan, 852-8501
        • Recruiting
        • Nagasaki University Hospital
        • Contact:
        • Principal Investigator:
          • Yasushi Miyazaki, MD
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8603
        • Recruiting
        • Nippon Medical School Hospital
        • Contact:
        • Principal Investigator:
          • Hiroki Yamaguchi, MD
  • Singapore
      • Singapore, Singapore, 119074
        • Recruiting
        • National University Cancer Institute
        • Contact:
        • Principal Investigator:
          • Melissa Ooi, MD
  • South Korea
      • Hwasun, South Korea
        • Recruiting
        • Chonnam National University Hwasun Hospital
        • Contact:
        • Principal Investigator:
          • Jae-Sook Ahn, MD
      • Seoul, South Korea
        • Recruiting
        • Samsung Medical Center
        • Contact:
        • Principal Investigator:
          • Jun Jo Hang, MD
      • Seoul, South Korea
        • Recruiting
        • Seoul National University Hospital
        • Contact:
        • Principal Investigator:
          • Dong-Yeop Shin, MD
      • Seoul, South Korea
        • Recruiting
        • The Catholic University of Korea
        • Contact:
        • Principal Investigator:
          • HeeJe Kim, MD
  • Spain
      • Albacete, Spain
        • Recruiting
        • Hospital General Universitario De Albacete
        • Contact:
        • Principal Investigator:
          • Jesus Lorenzo Algarra, MD
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
      • Barcelona, Spain
        • Recruiting
        • Institut Catala d'Oncologia
        • Contact:
        • Principal Investigator:
          • Susana Vives Polo, MD
      • Cáceres, Spain
        • Recruiting
        • Hospital San Pedro de Alcantara
        • Contact:
        • Principal Investigator:
          • Juan Miguel Bergua Burgues, MD
      • Las Palmas, Spain
        • Recruiting
        • Hospital Universitario de Gran Canaria Dr. Negrin
        • Contact:
        • Principal Investigator:
          • Carlos Rodriguez Medina, MD
      • Madrid, Spain
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Adolfo de la Fuente Burguera, MD
        • Contact:
      • Oviedo, Spain
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
        • Principal Investigator:
          • Teresa Bernal del Castillo, MD
      • Salamanca, Spain
        • Recruiting
        • Hospital Universitario de Salamanca
        • Contact:
        • Principal Investigator:
          • Maria-Belen Vidriales Vicente, MD
      • Santander, Spain
      • Santiago de Compostela, Spain
      • Valencia, Spain
        • Recruiting
        • Hospital Universitario y Politécnico La Fe
        • Contact:
        • Principal Investigator:
          • Paul Montesinos, MD
  • Switzerland
      • Basel, Switzerland, 4031
        • Not yet recruiting
        • University Hospital Basel
      • Bern, Switzerland, 3010
        • Not yet recruiting
        • University Hospital Bern Inselspital
      • Zurich, Switzerland, 8091
        • Not yet recruiting
        • Universitaetsspital Zuerich - Haematology
  • Taiwan
      • Taichung, Taiwan
        • Recruiting
        • Taichung Veterans General Hospital
        • Contact:
        • Principal Investigator:
          • Huey-En Tzeng, MD
      • Tainan, Taiwan
        • Recruiting
        • National Cheng Kung University Hospital
        • Contact:
        • Principal Investigator:
          • Tsai-Yun Chen, MD
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
        • Principal Investigator:
          • Shang-Ju Wu, MD
  • United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • University Hospitals of Birmingham Centre for Clinical Hematology
        • Contact:
      • Bristol, United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
      • London, United Kingdom
      • London, United Kingdom
        • Recruiting
        • University College London Hospitals NHS Foundation Trust
        • Contact:
      • London, United Kingdom
      • Manchester, United Kingdom
        • Recruiting
        • Christie Hospital NHS Foundation Trust
        • Contact:
      • Oxford, United Kingdom
      • Stoke-on-Trent, United Kingdom
        • Not yet recruiting
        • University Hospitals of North Midlands NHS Foundation Trust
        • Contact:
      • Sutton, United Kingdom
  • United States
    • California
      • Newport Beach, California, United States, 92663
        • Recruiting
        • Hoag Family Cancer Center
        • Contact:
        • Principal Investigator:
          • Benjamin Goldenson, MD
      • Palo Alto, California, United States, 94304
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Colorado Blood Cancer Institute
        • Principal Investigator:
          • Alireza Eghtedar, MD
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Not yet recruiting
        • Georgetown Lombardi Comprehensive Cancer Center
        • Contact:
          • SMPA Investigative Site
          • Phone Number: 508-481-6700
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
        • Principal Investigator:
          • Justin Watts, MD
      • Miami, Florida, United States, 33176
        • Not yet recruiting
        • Miami Cancer Institute
        • Contact:
          • SMPA Investigative Site
          • Phone Number: 508-481-6700
      • Tampa, Florida, United States, 33612
        • Not yet recruiting
        • Moffitt Cancer Center
        • Contact:
          • SMPA Investigative Site
          • Phone Number: 508-481-6700
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza, MD
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland
        • Principal Investigator:
          • Maria Baer, MD
        • Contact:
      • Baltimore, Maryland, United States, 20016
        • Recruiting
        • Sibley Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Mark Levis
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Main Center
        • Contact:
        • Principal Investigator:
          • Mark Levis, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Andrew Brunner, MD
        • Contact:
      • Boston, Massachusetts, United States, 02111
        • Withdrawn
        • Tufts University
    • New Jersey
      • Morristown, New Jersey, United States, 07960
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Principal Investigator:
          • Neil Palmisiano, MD
        • Contact:
    • New York
      • Buffalo, New York, United States, 14203
        • Recruiting
        • Roswell Park Comprehensive Cancer Center
        • Principal Investigator:
          • Eunice Wang, MD
        • Contact:
      • New York, New York, United States, 10029
        • Completed
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • Completed
        • Columbia University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Recruiting
        • UNC Hospital
        • Principal Investigator:
          • Joshua Zeidner, MD
        • Contact:
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University
        • Contact:
        • Principal Investigator:
          • Harry Erba, MD
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Atrium Wake Forest Baptist Medical Center
        • Principal Investigator:
          • Timothy Pardee, MD
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Kristen Browning, MD
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Oncology Associates of Oregon
        • Principal Investigator:
          • Luke Fletcher, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Gina Keiffer, MD
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Allegheny Health Network
        • Contact:
        • Principal Investigator:
          • Salman Fazal, MD
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Praneeth Baratam, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MDACC
        • Principal Investigator:
          • Naval Daver, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
        • Principal Investigator:
          • Paul Shami, MD
      • Salt Lake City, Utah, United States, 84143
        • Recruiting
        • Intermountain Healthcare
        • Contact:
        • Principal Investigator:
          • Bradley Hunter, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Michael Keng, MD
        • Contact:
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Mitul Gandhi, MD
        • Contact:
      • Norfolk, Virginia, United States, 23502

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

For patients in Phase I:

  1. 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):

    1. Patients with MDS must have bone marrow blasts ≥ 5%

    2. 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):

    3. 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
    4. Have measurable disease as defined in the protocol

    5. 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):

    6. Have MLLr or NPM1m.

      For patients with relapsed/refractory AML in the gilteritinib combination cohort (in countries and sites where permitted):

    7. 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:

    8. Must have ≥5% blasts in bone marrow by morphologic assessment

    9. Must not have received prior treatment with a menin inhibitor

      For patients with newly diagnosed AML:

    10. Must have AML as defined by WHO 2022 criteria with a documented MLLr or NPM1m (patients with AML characterized by MLL partial tandem duplications, MLL deletions, or trisomy 11 are not eligible)
    11. Must not have received treatment for AML with the exception of hydroxyurea for control of white blood cell counts.

    For patients in Phase 2:

  2. Have a confirmed diagnosis of relapsed AML or ALL according to WHO 2022 classification, as determined by pathology review at the treating institution, and who have ≥5% blasts by morphologic assessment in the bone marrow. Patients with extramedullary disease or peripheral blasts as the only manifestation of relapse are not eligible. Patients must have received clinically applicable standard therapies with confirmed survival benefit. Patients must not have had prior exposure to a menin inhibitor.

  3. Have a documented KMT2A (MLL)-fusion assessed at relapse or immediately prior to the determination of refractory status. KMT2A genetic alterations other than fusions (eg, KMT2A-PTD, amplification, point mutation) are not permitted.

    For all patients:

  4. Be > 18 years of age. For countries and sites where approved, for DSP-5336 monotherapy, acute leukemia patients ≥12 years of age who weigh ≥40 kg may be enrolled.
  5. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  6. For monotherapy, WBC below 30,000/μ at enrollment. For the combination arms, WBC count must be below 25,000/uL at enrollment and prior to starting treatment. (Hydroxyurea and steroids for cytoreduction purposes are allowed prior to enrollment and during study treatment)
  7. Clearance of creatinine level ≥ 50 ml/min, assessed by the CPK-EPI formula (2021 version and Cystatin C not required)
  8. Total bilirubin ≤1.5 the upper limit of normal (ULN) (or ≤2.0 ULN for patients with known Gilbert's syndrome)
  9. Aspartate aminotransferase (AST) ≤3.0 times ULN
  10. Alanine aminotransferase (ALT) ≤3.0 times ULN
  11. Any prior treatment-related toxicities resolved to Grade ≤1 prior to enrollment, with the exception of Grade ≤2 alopecia or neuropathy
  12. Be willing to attend study visits as required by the protocol
  13. Have an estimated life expectancy ≥3 months, based on the investigator's assessment
  14. Females of childbearing potential must have a negative serum pregnancy test. Females of childbearing potential are defined as women who have (1) experienced menarche and have not undergone sterilization procedures (hysterectomy, or bilateral oophorectomy), or have (2) not experienced menopause as defined in the protocol.
  15. All men and all women of childbearing potential and male patients' partners who are women of childbearing potential are required to use a highly effective method of contraception during the study and for 6 months (for females and males alike) after the last dose of study drug. Further guidelines noted in protocol.
  16. Have AML/ALL/MDS/MM bone marrow material suitable for genomic analysis of AML,ALL, MDS, or MM genetic alterations. Note: If a bone marrow material is insufficient, an alternative suitable tissue (ex: peripheral blood) must be provided.

Exclusion Criteria:

  1. Has a left ventricular ejection fraction (LVEF) <50%, as determined by ECHO
  2. Histological diagnosis of acute promyelocytic leukemia
  3. Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336

  4. 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.

  5. 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.
  6. 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.
  7. Had major surgery within 28 days prior to the first dose of DSP-5336
  8. Has active central nervous system leukemia (prophylactic intrathecal chemotherapy is allowed).
  9. 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.
  10. 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
  11. 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
  12. 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

  13. 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.

  14. Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication
  15. Have cognitive, psychological, or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures
  16. Are pregnant or breastfeeding or planning to become pregnant. Note: Patients who are breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose of any study drugs and do not feed the baby with breast milk expressed after receiving the first dose of any study drugs. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug

  17. Have any history or complication of interstitial lung disease (for sites in Japan in Phase 1 dose escalation).

    For clinical sites in the EU, have a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥ 2 non-infectious pneumonitis within 6 months of starting study treatment.

  18. Have a history of Torsades de Pointes
  19. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP-5336
  20. Have plasma cell leukemia (>2.0 x 109 /L plasma cells in blood by standard differential) (for patients with MM)
  21. For patients intending to enroll into the combination cohort with gilteritinib: Patients must be gilteritinib-naïve or sensitive and have not received a FLT3 inhibitor in the relapsed refractory setting (prior FLT3 inhibitor in front line therapy is allowed)
  22. Have a known intolerance of hypersensitivity reaction to components of the investigational medicinal product
  23. For clinical sites in the UK: In Arm E (DSP-5336 + venetoclax/azacitidine), have received a live vaccine within 30 days prior to the first dose of DSP-5336

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2 - Arm G
R/R AML with MLLr
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 2 - Arm H
R/R AML with NPM1m
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 2 - Arm I
R/R ALL with MLLr
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 1 - Arm A
R/R acute leukemia without CYP3A4 inhibitor azoles
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 1 - Arm B
R/R acute leukemia with CYP3A4 inhibitor azoles
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Experimental: Phase 1 - Arm C
High-risk MDS after HMA
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 1 - Arm D
Patients with refractory MM
Drug: Enzomenib
DSP-5336 orally
Experimental: Phase 1 - Arm E
R/R AML with NPM1m or KMT2Ar
Drug: Enzomenib
DSP-5336 orally
Drug: Venetoclax
Venetoclax orally
Drug: Azacitidine (AZA)
Azacitidine orally
Experimental: Phase 1 - Arm F
R/R AML with FLT3m + NPM1m or KMT2Ar
Drug: Enzomenib
DSP-5336 orally
Drug: Gilteritinib
Gilteritinib orally
Experimental: Phase 2 - Arm J
R/R acute leukemia with MLLr
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Experimental: Phase 2 - Arm K
R/R AML with NPM1m
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Experimental: Phase 1 - Arm L
Newly diagnosed AML KMT2Ar FIT or UNFIT
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Drug: Venetoclax
Venetoclax orally
Drug: Azacitidine (AZA)
Azacitidine orally
Experimental: Phase 1 - Arm M
Newly diagnosed AML NPM1m UNFIT only
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Drug: Venetoclax
Venetoclax orally
Drug: Azacitidine (AZA)
Azacitidine orally
Experimental: Phase 1 - Arm N
Newly diagnosed AML with KMT2Ar or NPM1m
Drug: Enzomenib
DSP-5336 orally
Drug: azoles
Posaconazole, Voriconazole, or Fluconazole
Drug: Intensive chemotherapy with 7 + 3
chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events and serious adverse events in Phase 1
Time Frame: 30 days from last dose
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)
Time Frame: Within 4 months from first dose
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
Time Frame: Within 4 months from first dose
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
Time Frame: Within 4 months from first dose
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
Time Frame: Within 4 months from the first dose
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
Time Frame: Within 4 months from first dose
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
Time Frame: Approximately 6 months after first dose
Disease response defined by the FDA guidance and ELN2017
Approximately 6 months after first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The maximum observed concentration (Cmax) of of DSP-5336, venetoclax and gilteritinib
Time Frame: Approximately 3 months after first dose
Cmax of DSP-5336, venetoclax and gilteritinib are calculated from the individual concentration time curve
Approximately 3 months after first dose
Area under the plasma concentration vs. time curve (AUClast) of DSP-5336, venetoclax and gilteritinib
Time Frame: Approximately 3 months after first dose
The determination of AUClast using the linear/log trapezoidal rule
Approximately 3 months after first dose
T(1/2) of DSP-5336, venetoclax and gilteritinib
Time Frame: Approximately 3 months after first dose
Elimination half-life (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
Time Frame: Approximately 3 months after first dose
Cmax of DSP-5336 is calculated from the individual concentration time curve
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
Time Frame: Approximately 3 months after first dose
The determination of AUClast using the linear/log trapezoidal rule
Approximately 3 months after first dose
t(1/2) of of DSP-5336 in the presence of high fat meal
Time Frame: Approximately 3 months after first dose
Elimination half-life (t[1/2]) of DSP-5336
Approximately 3 months after first dose
Number of patients achieving complete response (CR) in the 7+3 arm in Phase 1
Time Frame: Approximately 6 months after first dose
Disease response defined by the ELN2017
Approximately 6 months after first dose
Number of patients achieving CRc, which means complete response (CR), complete response with partial hematologic recovery (CRh) or complete response with incomplete count recovery (CRi) in the 7+3 arm in Phase 1
Time Frame: Approximately 6 months after first dose
Disease response defined by the FDA guidance and ELN2017
Approximately 6 months after first dose
Number of patients with adverse events and serious adverse events in Phase 2
Time Frame: 30 days from the last dose
Assessment of safety of DSP-5336 administered in patients with advanced hematologic malignancies by reporting of adverse events and serious adverse events in Phase 2
30 days from the last dose
Number of patients achieving CRc, which means complete response (CR), complete response with partial hematologic recovery (CRh) or complete response with Incomplete count recovery (CRi) in Phase 2
Time Frame: Approximately 6 months after first dose
Disease response defined by the FDA guidance and ELN2027
Approximately 6 months after first dose
Number of patients achieving ORR, which means complete response (CR), complete response with Incomplete count recovery (CRi) or MFLS (Morphologic leukemia-free state) in Phase 2
Time Frame: Approximately 6 months after first dose
Disease response defined by ELN2027
Approximately 6 months after first dose
Event-Free Survival in Phase 2
Time Frame: Approximately 6 months after first dose
The time period from treatment initiation to hematologic relapse, progressive disease or death
Approximately 6 months after first dose
Overall Survival in Phase 2
Time Frame: Two years after the end of treatment
The time period from treatment initiation to death
Two years after the end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sumitomo Pharma America, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2022

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

July 26, 2021

First Submitted That Met QC Criteria

July 26, 2021

First Posted (Actual)

August 3, 2021

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DSP-5336-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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