RECRUITING

A Study of DSP-5336 in Relapsed/Refractory AML/ ALL With or Without MLL Rearrangement or NPM1 Mutation

Conditions

Leukemia, Myeloid, Acute Leukemia, Lymphocytic, Acute Relapsed or refractory AML MLLr Menin NPM1m KMT2A

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of DSP-5336 in Adult Patients With Acute Leukemia and Other Selected Hematologic Malignancies, With and Without Mixed Lineage Leukemia (MLL) Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Quick Facts

Study Start:2022-02-28

Study Completion:2027-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04988555

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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 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 1. Have MLLr or NPM1m. 2. Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836. 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 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.	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). 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. 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). 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

Inclusion Criteria

Exclusion Criteria

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
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
1. Have MLLr or NPM1m.
2. Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
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
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.

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). 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.
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).
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

Contacts and Locations

Study Contact

Matt Hitron, MD

CONTACT

508-481-6700

matthew.hitron@us.sumitomo-pharma.com

Tomoko Kuwabara

CONTACT

tomoko.kuwabara@us.sumitomo-pharma.com

Study Locations (Sites)

Hoag Family Cancer Center

Newport Beach, California, 92663

United States

Colorado Blood Cancer Institute

Denver, Colorado, 80218

United States

University of Miami

Miami, Florida, 33136

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

Pittsburg, 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

Collaborators and Investigators

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 Registration Dates

Study Start Date2022-02-28

Study Completion Date2027-10-31

Study Record Updates

Study Start Date2022-02-28

Study Completion Date2027-10-31

Terms related to this study

Keywords Provided by Researchers

Relapsed or refractory AML
MLLr
Menin
NPM1m
KMT2A

Additional Relevant MeSH Terms

Leukemia, Myeloid, Acute
Leukemia, Lymphocytic, Acute