A Study of DSP-5336 in Relapsed/Refractory AML/ ALL With or Without MLL Rearrangement or NPM1 Mutation
NCT ID: NCT04988555
Last Updated: 2025-04-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
362 participants
INTERVENTIONAL
2022-02-28
2027-10-31
Brief Summary
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Detailed Description
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Phase 2 dose-expansion will further evaluate the safety and clinical activity of Enzomenib (DSP-5336) monotherapy in patients with relapsed/refractory AML who have MLLr or NPM1m, and relapsed/refractory ALL who have MLLr.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase 1 - Arm A
Patients not taking antifungals within 7 days of study entry
Enzomenib
DSP-5336 orally
Phase 1 - Arm B
Patients receiving antifungals that are moderate to strong cytochrome CYP3A4/5 inhibitors (i.e. posaconazole, voriconazole, or fluconazole).
Enzomenib
DSP-5336 orally
azoles
Posaconazole, Voriconazole, or Fluconazole
Phase 1 - Arm C
Patients with MDS
Enzomenib
DSP-5336 orally
Phase 1 - Arm E
Patients with AML
Enzomenib
DSP-5336 orally
Venetoclax
Venetoclax orally
Azacitidine (AZA)
Azacitidine orally
Phase 1 - Arm F
Patients with AML
Enzomenib
DSP-5336 orally
Gilteritinib
Gilteritinib orally
Phase 2 - Arm G
R/R AML with MLLr
Enzomenib
DSP-5336 orally
Phase 2 - Arm H
R/R AML with NPM1m
Enzomenib
DSP-5336 orally
Phase 2 - Arm I
R/R ALL with MLLr
Enzomenib
DSP-5336 orally
Interventions
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Enzomenib
DSP-5336 orally
azoles
Posaconazole, Voriconazole, or Fluconazole
Venetoclax
Venetoclax orally
Gilteritinib
Gilteritinib orally
Azacitidine (AZA)
Azacitidine orally
Eligibility Criteria
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Inclusion Criteria
For patients with MDS (US only):
1. Patients with MDS must have IPSS-R risk categorization of "high" or "very high" at initial diagnosis or at study entry and have bone marrow blasts ≥ 5% (which is the definition of high-risk MDS in this study)
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 (US only):
1. 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
2. Have measurable disease as defined in the protocol
3. 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):
1. Have MLLr or NPM1m.
For patients with relapsed/refractory AML in the gilteritinib combination cohort (in countries and sites where permitted):
2. Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
Patients in the Phase 2 dose expansion portion of the study must have a confirmed diagnosis of relapsed AML or ALL as determined by pathology review at the treating institution, and who have ≥5% blasts by morphologic assessment in the bone marrow and failed available standard therapies known to be active for their AML (Arm G and H) or ALL (Arm I). If the primary disease is a transformation from MDS or other hematologic malignancies, patients need to receive available standard therapies for acute leukemia before enrolling this trial. Participants who are candidates for stem cell transplantation must have been offered this therapeutic option. Patients with extramedullary disease or peripheral blasts as the only manifestation of relapse are not eligible.
1. Patients must not have had prior exposure to a menin inhibitor
2. Patients for Arms G and H are limited to a total of 3 prior lines of therapy, with induction chemotherapy, consolidation chemotherapy, and stem cell transplantation with or without subsequent maintenance treatment considered to be 1 line.
3. Have a documented KMT2A (MLL)-fusion for Arm G and I or NPM1 mutation for Arm H assessed at relapse or immediately prior to the determination of refractory status. For Arms G and I, KMT2A genetic alterations other than fusions (eg, KMT2A-PTD, amplification, point mutation) are not permitted.
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. ECOG \< 2; For Phase 2 only, patients must have an ECOG performance status 0 or 1.
6. For monotherapy, WBC below 30,000/μ. 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 (CLcr) level ≥ 50 ml/min, assessed by the Cockcroft-Gault formula
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.
15. Must agree to use a highly effective contraception method or 2 acceptable methods of birth control (each partner must use one method) or use prevention of pregnancy measures (ie, agreement to refrain completely from heterosexual intercourse) during the study and for 6 months (for females and males alike) after the last dose of study drug, if male or female patient is of child-producing potential
For sites in Japan only: Implantable hormonal contraceptives, a diaphragm with spermicide, cervical cap with spermicide and contraceptive sponge (spermicide is already in the contraceptive sponge) included in the barrier contraceptive method are not approved and cannot be used in Japan.
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
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). Note: In case of bundle branch block, QT interval correction can be performed.
5. Has an active anduncontrolled, 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. Received immunotherapy, including tumor vaccines and checkpoint inhibitors, within 42 days prior to the first dose of DSP-5336
8. Had major surgery within 28 days prior to the first dose of DSP-5336
9. Has active central nervous system leukemia. Patients with a history of any CNS leukemia involvement are excluded from Phase 2 Arms G and H.
10. 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. Patients who have received \>1 prior HSCT are excluded from Phase 2 Arms G and H.
11. 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
12. 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 14 days or 5 half-lives, whichever is shortest, prior to the first dose of DSP-5336
13. 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
14. 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.
15. 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
16. Have cognitive, psychologic, or psychosocial impediment that would impair the ability of the patient o 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
17. 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
18. Have any history or complication of interstitial lung disease (for sites in Japan in Phase 1 dose escalation only).
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.
19. Have a history of Torsades de Pointes
20. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP-5336
21. Have plasma cell leukemia (\>2.0 x 109 /L plasma cells in blood by standard differential) (for patients with MM only)
22. 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)
23. Have a known intolerance of hypersensitivity reaction to components of the investigational medicinal product
24. Patients with LDH \>500 U/L (\>8.3 µkat/L) are excluded from Phase 2 Arms G and H
18 Years
ALL
No
Sponsors
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Sumitomo Pharma America, Inc.
INDUSTRY
Responsible Party
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Locations
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Hoag Family Cancer Center
Newport Beach, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
University of Miami
Miami, Florida, United States
Northwestern
Chicago, Illinois, United States
Sibley Memorial Hospital
Baltimore, Maryland, United States
University of Maryland
Baltimore, Maryland, United States
Johns Hopkins Main Center
Baltimore, Maryland, United States
Tufts University
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Atlantic Health
Morristown, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Mount Sinai Hospital
New York, New York, United States
Columbia University
New York, New York, United States
UNC Hospital
Chapel Hill, North Carolina, United States
Duke University
Durham, North Carolina, United States
Atrium Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Oncology Associates of Oregon
Eugene, Oregon, United States
Sidney Kimmel Comprehensive Cancer Center
Philadelphia, Pennsylvania, United States
Allegheny Health Network
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
TriStar Centennial Medical Center
Nashville, Tennessee, United States
MDACC
Houston, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Intermountain Healthcare
Salt Lake City, Utah, United States
University of Virginia
Charlottesville, Virginia, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
ZNA Cadix
Antwerp, , Belgium
UZ Ghent
Ghent, , Belgium
University Hospitals Leuven
Leuven, , Belgium
AZ Delta
Roeselare, , Belgium
Tom Baker Cancer Center
Calgary, Alberta, Canada
University of Alberta
Edmonton, , Canada
Centre Hospitalier Universitaire d'Angers
Angers, , France
Hopital Avicenne
Bobigny, , France
Centre Hospitalier Le Mans
Le Mans, , France
Hopital Claude Huriez
Lille, , France
Centre Hospitalier Universitaire de Limoges
Limoges, , France
Hospices Civils de Lyon
Lyon, , France
Institut Paoli-Calmettes
Marseille, , France
CHU de Nice - Hôpital l'Archet 1
Nice, , France
Hopital Saint-Louis
Paris, , France
CHU Bordeaux
Talence, , France
Institut Gustave Roussy
Villejuif, , France
Alma Mater Studiorum University Of Bologna
Bologna, , 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
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, Japan
University of Fukui Hospital
Yoshida-gun, Fukui, Japan
Fukushima Medical University Hospital
Fukushima, Fukushima, Japan
Tokai University Hospital
Isehara-shi, Kanagawa, Japan
Nagasaki University Hospital
Nagasaki, Nagasaki, Japan
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, Japan
Kyushu University Hospital
Fukuoka, , Japan
Hokkaido University Hospital
Hokkaido, , Japan
Tohoku University Hospital
Miyagi, , Japan
Okayama University Hospital
Okayama, , Japan
Osaka University Hospital
Osaka, , Japan
National University Cancer Institute
Singapore, , 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
Fundacion Instituto de Investigacion Marques de Valdecilla
Cantabria, , 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
Complexo Hospitalario Universitario De Santiago
Santiago de Compostela, , Spain
Hospital Universitario y Politecnico La Fe
Valencia, , Spain
Taichung Veterans General Hospital
Taichung, , Taiwan
National Cheng Kung University Hospital
Tainan City, , 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
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
Countries
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Central Contacts
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Facility Contacts
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Alireza Eghtedar, MD
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
Cristina Papayannidis, MD
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
SMPA Investigative Site
Role: primary
Other Identifiers
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DSP-5336-101
Identifier Type: -
Identifier Source: org_study_id
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