Trial record 2 of 4 for:    DS-3032

Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-3032b in Hematological Malignancies

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. Identifier: NCT02319369
Recruitment Status : Recruiting
First Posted : December 18, 2014
Last Update Posted : May 31, 2018
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This will be a Phase 1, open-label study of DS-3032b to assess its safety and tolerability and identify a Maximum Tolerated Dose (MTD)/tentative Recommended Phase II Dose (RP2D) in subjects with refractory or relapsed Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) in blast phase, or high risk MDS in Part 1-Dose Escalation and refractory or relapsed AML or high risk Myelodysplastic Syndrome (MDS) in Part 2-Dose Expansion.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Chronic Myelogenous Leukemia Myelodysplastic Syndrome Drug: DS-3032b Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of DS-3032b, an Oral Murine Double Minute (mdm2) Oncogene Inhibitor, in Subjects With Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) in Blast Phase, or High-Risk Myelodysplastic Syndrome (MDS)
Study Start Date : November 2014
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : April 2019

Arm Intervention/treatment
Experimental: DS-3032b
DS-3032b will be administered as a single oral capsule or as a combination of multiple oral capsules containing 5 mg, 20 mg, 80 mg, and/or 200 mg DS-3032b
Drug: DS-3032b
DS-3032b will be administered as a single oral capsule or as a combination of multiple oral capsules containing 5 mg, 20 mg, 80 mg, and/or 200 mg DS-3032b

Primary Outcome Measures :
  1. number and severity of adverse events [ Time Frame: 6 months ]
    To assess the safety and tolerability of DS 3032b in subjects with refractory or relapsed AML or ALL, CML in blast phase, or high risk MDS.

  2. maximum tolerated dose [ Time Frame: 2 months ]
    To determine the maximum tolerated dose (MTD) or tentative recommended Phase 2 dose (RP2D) of DS-3032b estimated by the modified continuous reassessment method (mCRM) using a Bayesian logistic regression model (BLRM), and on an overall assessment of safety data from subsequent cycles and drug exposure/Pharmacodynamic (PDy) response information collected at all different doses tested

Secondary Outcome Measures :
  1. pharmacokinetic profile of DS-3032b (Cmax, Tmax, and daily exposure) [ Time Frame: 28 days ]
    To evaluate the Cmax, Tmax, and daily exposure of DS-3032a (the free form of DS-3032b) following single and multiple dosing

  2. change in macrophage inhibitory cytokine-1 (MIC-1) levels [ Time Frame: 28 days ]
    To evaluate the pharmacodynamic (PDy) effect of DS-3032b on macrophage inhibitory cytokine-1 (MIC-1) levels in serum.

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

Inclusion Criteria:

  • Has one of the following diagnoses: Subjects must have refractory or relapsed AML or ALL, CML in blast phase, or high risk MDS (defined by Revised International Prognostic Scoring System [IPSS-R] score as High or Very High for inclusion in Part 1 of the study. Subjects must have refractory or relapsed AML or high-risk MDS (defined by IPSS-R score as High or Very High for inclusion in Part 2 of the study.
  • Man or woman >= 18 years old.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  • Has adequate renal function, defined as: Creatinine clearance >=60 mL/min, as calculated using the modified Cockcroft Gault equation, ([{140 - age in years} × {actual weight in kg}] divided by [{72 × serum creatinine in mg/dL} multiply by 0.85 if female]), OR creatinine =< 1.5 X ULN
  • Has adequate hepatic function, defined as:
  • AST/ALT =<3 X ULN; -Bilirubin =<1.5 X ULN, unless resulting from hemolysis
  • Has adequate blood clotting function, defined as: - International normalized ratio and activated partial thromboplastin time =<1.5 XULN
  • Subject is able to provide written informed consent, comply with protocol visits and procedures, and take oral medication, and does not have any active infection or comorbidity that would interfere with therapy.
  • Subject (male and female) of childbearing/ reproductive potential must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug.
  • Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects).
  • Subject must sign and date an Institutional Review Board-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests.
  • Able and willing to provide bone marrow biopsies/aspirates as requested by the protocol.
  • Is willing to undergo malignancy genotyping for TP53 gene mutation, insertion, or deletion at screening.
  • Has a life expectancy of at least 3 months.

Exclusion Criteria:

  • Has a diagnosis of acute promyelocytic leukemia.
  • Has a malignancy that contains a non synonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening.
  • Presence of central nervous system involvement of leukemia or a history of primary central nervous system leukemia.
  • Has a second concurrent primary malignancy that required active treatment within the previous 2 years, except for localized cancers that have apparently been cured, such as non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.
  • Any condition that would preclude adequate absorption of DS-3032b, including refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, and/or graft-versus-host disease (GVHD) affecting the gut.
  • Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
  • Has a concomitant medical condition that would in the opinion of the Investigator increase the risk of toxicity.
  • Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4, Grade =<1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per discretion of the Investigator and Sponsor (eg, Grade 2 chemotherapy-induced neuropathy).
  • Has received Hematopoietic Stem Cell Transplantation (HSCT) within 60 days of the first dose of DS-3032b, is on immunosuppressive therapy post-HSCT at the time of screening, or has clinically significant GVHD (use of topical steroids for ongoing skin GVHD will be permitted). Subjects must have a washout period of >=2 weeks or at least 4 half-lives from their last systemic immunosuppressive treatment for GVHD.
  • Is receiving concomitant treatment with a strong inhibitor or inducer of CYP3A4/5.
  • Received any therapies intended to treat malignancy within 14 days of first receipt of DS-3032b (except for hydroxyurea, which must be discontinued at least 48 hours prior to study treatment).
  • Had major surgery within 4 weeks prior to study drug treatment.
  • Participated in a therapeutic clinical study within 3 weeks before study drug treatment, or current participation in other therapeutic investigational procedures.
  • Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is >450 ms for males or >470 ms for females based on triplicate electrocardiograms (ECGs).
  • Pregnant or breastfeeding.
  • Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
  • Prior treatment with an MDM2 inhibitor.

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 identifier (NCT number): NCT02319369

Contact: Andrew Ruwe, PhD 513-579-9911 ext 2353

United States, California
City of Hope National Medical Center Completed
Duarte, California, United States, 91010
University of California San Francisco Medical Center Active, not recruiting
San Francisco, California, United States, 94143
United States, Texas
M D Anderson Recruiting
Houston, Texas, United States, 77031
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo, Inc. Identifier: NCT02319369     History of Changes
Other Study ID Numbers: DS3032-A-U102
First Posted: December 18, 2014    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address:
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders