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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04988555
Recruitment Status : Recruiting
First Posted : August 3, 2021
Last Update Posted : June 1, 2022
Sponsor:
Information provided by (Responsible Party):
Sumitomo Pharma Oncology, Inc.

Brief Summary:
A Phase 1/2 dose escalation / dose expansion study of DSP 5336 in patients with relapsed or refractory AML.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Leukemia, Lymphocytic, Acute Drug: DSP-5336 Phase 1 Phase 2

Detailed Description:

Phase 1 (dose escalation) will determine the recommended Phase 2 dose (RP2D) (i.e. the lowest dose of DSP 5336, that provides the maximum biologic and clinical effect, or the MTD, whichever is lower) in adult patients with relapsed or refractory AML or ALL.

Phase 2 dose-expansion will further evaluate the safety and clinical activity of DSP 5336 in adult patients with relapsed or refractory MLLr AML or NPM1m AML.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Bayesian Regression Model for Phase 1 dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Dose-Expansion Study of DSP-5336 in Adult Acute Leukemia Patients With and Without Mixed Lineage Leukemia (MLL)-Rearrangement or Nucleophosmin 1 (NPM1) Mutation
Actual Study Start Date : February 28, 2022
Estimated Primary Completion Date : January 2, 2025
Estimated Study Completion Date : February 1, 2025


Arm Intervention/treatment
Experimental: Phase 1 Arm A without Antifungals
Patients not taking antifungals within 7 days of study entry
Drug: DSP-5336
DSP-5336 orally

Experimental: Phase 1 Arm B with Antifungals
Patients receiving anti-fungals that are moderate to strong cytochrome CYP3A4/5 inhibitors (i.e. Posaconazole, voriconazole, fluconazole)
Drug: DSP-5336
DSP-5336 orally

Experimental: Phase 2 Arm A AML with MLL (KMT2A) gene rearrangements
Patients with R/R AML w/MLL (KMT2A) gene rearrangements
Drug: DSP-5336
DSP-5336 orally

Experimental: Phase 2 Arm B: AML with NPM1c mutations
Patients with R/R AML w/ NPM1c mutations
Drug: DSP-5336
DSP-5336 orally




Primary Outcome Measures :
  1. Phase I Assess the safety and tolerability of DSP-5336 in relapsed/refractory AML, ALL or acute leukemia of amibiguous lineage [ Time Frame: Approximately 2 months after first dose ]
    Occurrence of DLTs and frequency, duration and severity of TEAEs and SAEs assessed by NCI CTCAE v 5.0

  2. Phase I Determine the RP2D based on lowest dose of DSP-5336 that provides the maximum biologic and clinical effect, or the MTD, whichever is lower. [ Time Frame: Approximately 2 months after first dose ]
    Occurrence of DLTs and frequency, duration and severity of TEAEs and SAEs, plasma concentration-time profiles, changes in expression levels of biomarkers (gene expression levels).

  3. Phase 2 To evaluate clinical activity of DSP-5336 in adult patients with Relapsed /refractory AML who have MLL (KRMa gene rearrangement or NPM1 gene mutation) [ Time Frame: Approximately 6 months after first dose ]
    Occurrence of CR, CRh, CR with MRD, EFS, RFS, TTR, DOR.


Secondary Outcome Measures :
  1. Phase I Preliminary clinical activity of DSP-5336 in adult patients with AML or ALL [ Time Frame: Approximately 6 months after first dose ]
    Disease response as assessed by ELN 2017 criteria

  2. 2. Phase 2 To further assess safety and tolerability of DSP-5336 in adult patients with Relapsed /refractory AML [ Time Frame: Approximately 2 months after first dose ]
    Frequency, duration, and severity of TEAEs and SAEs assessed by NCI CTCAE v 5.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Have a diagnosis of relapsed or refractory AML or ALL or acute leukemia of ambiguous lineage for Phase I and for Phase 2 have a diagnosis of relapsed or refractory AML with MLLr or NPM1
  2. Be > 18 years of age or 20 years if required by local regulation
  3. ECOG < 2
  4. WBC below 30,000/μL (hydroxyurea allowed prior to initiation of the study treatment)
  5. Glomerular filtration rate (GFR) ≥ 50 ml/min, assessed by the Cockcroft-Gault formula
  6. Total bilirubin ≤1.5 the upper limit of normal (ULN) (or ≤2.0 ULN for patients with known Gilbert's syndrome)
  7. Aspartate aminotransferase (AST) ≤3.0 times ULN
  8. Alanine aminotransferase (ALT) ≤3.0 times ULN
  9. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia
  10. Have an estimated life expectancy ≥3 months, based on the investigator's assessment

Exclusion Criteria:

  1. Has a left ventricular ejection fraction (LVEF) <45%, as determined by ECHO
  2. Histological diagnosis of acute promyelocytic leukemia
  3. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP 5336
  4. Has had abnormal ECGs that are clinically significant, such as QT prolongation (QTc >450 msec for males and >470 msec for females, with QTc corrected according to Fridericia's formula [QTcF])
  5. Has an active, uncontrolled, bacterial, viral, or fungal infection requiring systemic therapy
  6. Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole, itraconazole and isavuconazole. Other antifungals that are used as standard of care to prevent or treat infections are permitted If a patient is on one of these excluded 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)
  7. Received immunotherapy, including tumor vaccines and checkpoint inhibitors, within 42 days prior to the first dose of DSP-5336
  8. Has been on other investigational treatment within the previous 4 weeks prior to the first dose of DSP-5336
  9. Had major surgery within 28 days prior to the first dose of DSP-5336
  10. Has active central nervous system leukemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04988555


Contacts
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Contact: Susan Smith 2104147702 susan.smith@oncology.sumitomo-pharma.com
Contact: Keiichi Saito 8572703610 keiichi.saito@oncology.sumitomo-pharma.com

Locations
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United States, Texas
MDACC Recruiting
Houston, Texas, United States, 77030
Contact: Naval Daver, MD    713-794-4392    NDaver@mdanderson.org   
Principal Investigator: Naval Daver, MD         
Japan
National Cancer Center Hospital East Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
Contact: Junichiro Yuda    04-7133-1111    jyuda@east.ncc.go.jp   
University of Fukui Hospital Recruiting
Yoshida-gun, Fukui, Japan, 910-1193
Contact: Naoko Hosono    0776-61-3111    hosono@u-fukui.ac.jp   
Fukushima Medical University Hospital Recruiting
Fukushima-shi, Fukushima, Japan, 960-1295
Contact: Takayuki Ikezoe    024-547-1111    ikezoet@fmu.ac.jp   
Tokai University Hospital Recruiting
Isehara-shi, Kanagawa, Japan, 259-1193
Contact: Kiyoshi Ando    0463-93-1121    andok@keyaki.cc.u-tokai.ac.jp   
Nagasaki University Hospital Recruiting
Nagasaki-shi, Nagasaki, Japan, 852-8501
Contact: Yasushi Miyazaki    095-819-7200    y-miyaza@nagasaki-u.ac.jp   
Sponsors and Collaborators
Sumitomo Pharma Oncology, Inc.
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Responsible Party: Sumitomo Pharma Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04988555    
Other Study ID Numbers: DSP-5336-101
First Posted: August 3, 2021    Key Record Dates
Last Update Posted: June 1, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sumitomo Pharma Oncology, Inc.:
Relapsed or refractory AML
MLLr
Menin
NPM1m
KMT2A
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases