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A Phase 1 Multiple Ascending Dose Study of DS-3201b in Japanese Subjects With Lymphomas

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ClinicalTrials.gov Identifier: NCT02732275
Recruitment Status : Recruiting
First Posted : April 8, 2016
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Brief Summary:
This will be a First-in-Human, Phase 1, multi-center, non-randomized, open label study of DS-3201b, Histone-lysine N-methyltransferase EZH1/2 dual inhibitor to assess its safety and tolerability, identify a maximum tolerated dose (MTD)/ tentative recommended phase 2 dose (RP2D), and assess its pharmacokinetic/dynamic properties in Japanese subjects with Non-Hodgkin's Lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma Lymphoma, B-cell Lymphoma, Follicular Adult T-Cell Leukemia Lymphoma (ATLL) Drug: DS-3201b Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Multiple Ascending Dose Study of DS-3201b in Japanese Subjects With Lymphomas
Study Start Date : March 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : April 2019


Arm Intervention/treatment
Experimental: DS-3201b Drug: DS-3201b



Primary Outcome Measures :
  1. number of dose limiting toxicities [ Time Frame: day 28 ]
    incidence of toxicities graded according to common terminology criteria for adverse events CTCAE

  2. maximum concentration Cmax [ Time Frame: day 28 ]
  3. time of maximum concentration Tmax [ Time Frame: day 28 ]
  4. area under the plasma concentration time curve up to the last quantifiable time AUClast [ Time Frame: day 28 ]
  5. area under the plasma concentration time curve during dosing interval AUCtau [ Time Frame: day 28 ]

Secondary Outcome Measures :
  1. response rate based on international consensus criteria [ Time Frame: week8, 16, 24, 32, 40 ]
    Response rate based on international consensus criteria according to Revised Response Criteria for Malignant Lymphoma or Definition, Prognostic Factors, Treatment, and Response Criteria of Adult T-cell Lymphoma-leukemia (ATLL)

  2. disease control rate based on international consensus criteria [ Time Frame: week8, 16, 24, 32, 40 ]
    Disease control rate based on international consensus criteria according to Revised Response Criteria for Malignant Lymphoma or Definition, Prognostic Factors, Treatment, and Response Criteria of ATLL

  3. the change of tri-methylated histone H3 lysine 27 (H3K27Me3) status by Immunohistochemistry [ Time Frame: day 28 ]
    the change of H3K27Me3 status by Immunohistochemistry to assess the DS-3201b effect on H3K27Me3 in blood/ skin biopsy as the exploratory pharmacodynamic biomarkers



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Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a cytologically or pathologically documented non hodgkin's lymphoma (NHL)
  • Subjects that has relapsed from or is refractory to standard treatment or for which no standard treatment is available.
  • Age ≥ 20 years at the time of the informed consent.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 at screening.
  • Has at least one target lesion.
  • Has adequate organ function, defined as:

Platelet count >= 75 x 109/L, Absolute neutrophil count >= 1.0 x 109/L,Creatinine clearance >= 60 mL/min, AST/ALT levels =< 3 x ULN, Bilirubin =< 1.5 x ULN.

ULN = upper limit normal AST = aspartate transaminase ALT = alanine transaminase

Exclusion Criteria:

  • Has a leukemia, such as precursor T-cell lymphoblastic leukemia, T-cell lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, T-cell prolymphocytic leukemia, or T-cell large granular lymphocytic leukemia
  • Has a history of central nervous system (CNS) symptoms, and are diagnosed with CNS lymphoma
  • Previously had (within 6 months before registration) or currently has any of the following diseases:

uncontrolled diabetes mellitus, cardiac failure (The New York Heart Association [NYHA] Functional Classification ≥ Class III), myocardial infarction, cerebral infarction, unstable angina, arrhythmia requiring treatment, coronary/peripheral bypass surgery, pulmonary thrombosis, uncontrolled deep vein thrombosis, clinically severe thromboembolic event, or autoimmune disease requiring treatment. Has a history of myocardial infarction and unstable angina within 6 months before registration; symptomatic congestive heart failure (CHF; NYHA classes III-IV); congenital long QT syndrome; or ventricular arrhythmia requiring treatment.

  • Grade 4 neuropathy
  • Has a QTcF prolongation to >450 ms based on triplicate ECG at screening.
  • Clinically severe infection that requires systemic administration of antibacterial or antiviral agents.
  • Positive for any of the following: active infection with human hepatitis B surface (HBs) antigen, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) antibody within 90 days before registration.
  • Positive for any of the following: human hepatitis B core (HBc) antibody, human HBs antibody with ≥ 2.1 log copies/mL hepatitis B virus (HBV)-DNA within 90 days before registration.
  • Has a concomitant neuropsychiatric disorder that would increase the risk of toxicity, in the opinion of the investigators.
  • Has a history of allogeneic hematopoietic stem cell transplantation.
  • Has received autologous hematopoietic stem cell transplantation within 12 weeks (84 days) of the start of study treatment.
  • Has received other investigational drugs within 4 weeks (28 days) of the start of study treatment.
  • Has received chemotherapy or immunotherapy (including targeted therapy with antibody or small molecule, retinoid therapy, and hormonal therapy) within 4 weeks (28 days) of the start of study treatment ( or within 12 weeks for anti CCR4 antibody or anti CD20 antibody).
  • Has received radiation therapy within 4 weeks (28 days) of the start of study treatment.
  • Has multiple primary malignancies, EXCEPT adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥5 years.
  • Has a concomitant treatment with strong/moderate inhibitors/inducers of cytochrome P450 3A4 (CYP3A4).
  • Is unwilling to use double-barrier contraceptive measures or avoid intercourse during the study and for at least 3 months after the last dose of DS-3201b.
  • Is a lactating mother, or pregnant as confirmed by pregnancy tests performed within 14 days before registration.
  • Prior treatment with other EZH inhibitors
  • Has a concomitant medical condition that would increase the risk of toxicity.

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): NCT02732275


Contacts
Contact: Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp

Locations
Japan
National Cancer Center Hospital Recruiting
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Global Clinical Leader, MD Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02732275     History of Changes
Other Study ID Numbers: DS3201-A-J101
First Posted: April 8, 2016    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Relapsed non-hodgkin lymphoma.
phase 1
oncology

Additional relevant MeSH terms:
Lymphoma
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, B-Cell
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia
Lymphoma, Non-Hodgkin