Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)

April 11, 2024 updated by: Daiichi Sankyo

Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects With Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)

This study will characterize the safety and clinical benefit of valemetostat tosylate in participants with relapsed/refractory peripheral T-cell lymphoma, including relapsed/refractory adult T-cell leukemia/lymphoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study was designed to evaluate the efficacy and safety of valemetostat tosylate monotherapy. The primary objective will evaluate objective response rate of valemetostat tosylate monotherapy as measured by blinded independent central review (BICR) in relapsed/refractory peripheral T-cell lymphoma.

Study Type

Interventional

Enrollment (Estimated)

148

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Richmond, Australia, 3121
        • Epworth Healthcare
  • Canada
      • Ottawa, Canada, K1H 8L6
        • Ottawa Hospital Research Institute
      • Toronto, Canada, M5G 1Z5
        • University Health Network Princess Margaret Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer - Vancouver Centre
  • France
      • Dijon, France, 21079
        • CHU de Dijon
      • Lille, France, 59037
        • CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang
      • Lyon, France, 69008
        • Centre Lyon Berard - Medical Oncology
      • Paris, France, 75010
        • APHP - Hopital Saint Louis
      • Paris, France, 75015
        • Hopital Necker
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier Lyon Sud - Hématologie
      • Toulouse, France, 31100
        • Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)
  • Germany
      • Halle, Germany, 06120
        • Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
  • Italy
      • Bergamo, Italy, 24127
        • ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
      • Bologna, Italy, 40138
        • A.O.di Bologna Policl.S.Orsola
      • Monza, Italy, 20900
        • PO San Gerardo, ASST Monza
      • Napoli, Italy, 80131
        • Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
      • Perugia, Italy, 06132
        • Ospedale S.Maria della Misericordia, AO di Perugia, Università degli Studi di Perugia
  • Japan
      • Fukuoka, Japan, 812-0054
        • Kyushu University Hospital
      • Kagoshima, Japan, 890-8520
        • Kagoshima University Hospital
      • Kyoto, Japan, 602-8566
        • University Hospital - Kyoto Prefectural University of Medicine
      • Nagasaki, Japan, 852-8501
        • Nagasaki University Hospital
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
    • Aichi
      • Nagoya, Aichi, Japan, 467-8602
        • Nagoya City University Hospital
      • Nagoya, Aichi, Japan, 460-0001
        • National Hospital Organization Nagoya Medical Center - Hematology
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital - Medical Oncology Center
    • Tokyo
      • Chuo Ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • Korea, Republic of
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center - Oncology
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital - Department of Internal
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center - Hematology-Oncology
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
  • Netherlands
      • Leiden, Netherlands, 2333ZA
        • Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)
      • Maastricht, Netherlands, 6229 HX
        • Universiteit Maastricht Academisch Ziekenhuis Maastricht
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08029
        • ICO Hospital Duran i Reynals
      • Madrid, Spain, 28040
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital - Internal Medicine
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital - Hematology And Oncology
      • Taoyuan City, Taiwan, 33305
        • Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology
  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • University College London Hospital
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham City Hospital - Clinical Haematology
      • Oxford, United Kingdom, OX3 7LE
        • Churchill Hospital
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Palo Alto, California, United States, 94304
        • Stanford University Medical Center - Cancer Clinical Trials Office - ONCOLOGY
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University - Feinberg School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55901
        • Mayo Clinic - Rochester
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center - John Theurer Cancer Center
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medicine
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center at Memorial Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Perelman Center for Advanced Medicine

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent
  • Participants ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2

  • Cohort 1 relapsed/refractory peripheral T-cell lymphoma (PTCL):

    • Diagnosis should be confirmed by the local pathologist; local histological diagnosis will be used for eligibility determination. Participants with the following subtypes of PTCL are eligible according to 2016 WHO classification prior to the initiation of study drug. Any T-cell lymphoid malignancies not listed are excluded. Eligible subtypes include:

      • Enteropathy-associated T-cell lymphoma
      • Monomorphic epitheliotropic intestinal T-cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Primary cutaneous γδ T-cell lymphoma
      • Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
      • PTCL, not otherwise specified
      • Angioimmunoblastic T-cell lymphoma
      • Follicular T-cell lymphoma
      • Nodal PTCL with T-follicular helper (TFH) phenotype
      • Anaplastic large cell lymphoma, ALK positive
      • Anaplastic large cell lymphoma, ALK negative
  • Cohort 2 relapsed/refractory adult T-cell leukemia/lymphoma (ATL) acute, lymphoma, or unfavorable chronic type. Relapsed/refractory ATL should be confirmed by the local pathologist; local diagnosis will be used for eligibility determination. The positivity of anti-human T-cell leukemia virus type 1 (HTLV-1) antibody will be locally determined for eligibility.
  • Must have at least one lesion which is measurable in 2 perpendicular dimensions on computed tomography (or magnetic resonance imaging) based on local radiological read

  • Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy.

    • Refractory is defined as:

      • Failure to achieve CR (or CRu for ATL) after first-line therapy
      • Failure to reach at least PR after second-line therapy or beyond

  • Must have at least 1 prior line of systemic therapy for PTCL or ATL.

    • Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
    • In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study. Below is a list of the key exclusion criteria:

  • Diagnosis of mycosis fungoides, Sézary syndrome and primary cutaneous ALCL, and systemic dissemination of primary cutaneous ALCL
  • Diagnosis of precursor T-cell leukemia and lymphoma (T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma), T-cell prolymphocytic leukemia, or T-cell large granular lymphocytic leukemia
  • Prior malignancy active within the previous 2 years except for locally curable cancer that is currently considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer.
  • Presence of active central nervous system involvement of lymphoma
  • History of autologous HCT within 60 days prior to the first dose of study drug
  • History of allogeneic HCT within 90 days prior to the first dose of study drug
  • Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment

  • Inadequate washout period from prior lymphoma-directed therapy before enrollment, defined as follows:

    • Prior systemic therapy (eg, chemotherapy, immunomodulatory therapy, or monoclonal antibody therapy) within 3 weeks prior or 5 half-lives of the drug, whichever is longer, to the first dose of study drug
    • Had curative radiation therapy or major surgery within 4 weeks or palliative radiation therapy within 2 weeks prior to the first dose of study drug

  • Uncontrolled or significant cardiovascular disease, including:

    • Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT corrected for heart rate using Fridericia's method >450 ms) (average of triplicate determinations)
    • Diagnosed or suspected long QT syndrome or known family history of long QT syndrome
    • History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
    • Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial fibrillation may be enrolled) or asymptomatic persistent ventricular tachycardia
    • Participant has clinically relevant bradycardia of <50 bpm, unless the participant has a pacemaker
    • History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers within 6 months prior to Screening
    • Myocardial infarction within 6 months prior to Screening
    • Angioplasty or stent craft implantation within 6 months prior to Screening
    • Uncontrolled angina pectoris within 6 months prior to Screening
    • New York Heart Association Class 3 or 4 congestive heart failure
    • Coronary/peripheral artery bypass graft within 6 months prior to Screening
    • Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg)
    • Complete left bundle branch block
  • History of treatment with other EZH inhibitors
  • Current use of moderate or strong cytochrome P450 (CYP)3A inducers
  • Systemic treatment with corticosteroids (>10 mg daily prednisone equivalents). Note: Short-course systemic corticosteroids (eg, prevention/treatment for transfusion reaction) or use for a non-cancer indication (eg, adrenal replacement) is permissible.
  • Known or suspected hypersensitivity to valemetostat tosylate or any of the excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma
Participants who will receive 200 mg/day valemetostat tosylate and had an eligible peripheral T-cell lymphoma subtype that was confirmed by independent hematopathology central review.
Drug: Valemetostat Tosylate
Oral administration of valemetostat tosylate at a dose of 200 mg once daily starting at Cycle 1, Day 1 (continuous for 28-day cycles), until disease progression or unacceptable toxicity
Other Names:
  • DS-3201b
Experimental: Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma
Participants who will receive 200 mg/day valemetostat tosylate and had an eligible adult T-cell leukemia/lymphoma subtype that was confirmed by the local pathologist/investigators and by documented positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibody.
Drug: Valemetostat Tosylate
Oral administration of valemetostat tosylate at a dose of 200 mg once daily starting at Cycle 1, Day 1 (continuous for 28-day cycles), until disease progression or unacceptable toxicity
Other Names:
  • DS-3201b

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: From baseline until disease progression or death (whichever occurs first), up to approximately 56 months
For the relapsed/refractory peripheral T-cell lymphoma (PTCL) cohort, objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), assessed by blinded independent central review (BICR), among participants with centrally confirmed PTCL eligible histology.
From baseline until disease progression or death (whichever occurs first), up to approximately 56 months
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2)
Time Frame: From the time the informed consent form is signed up to 30 days after last dose
Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), severe events (Grades 3 and 4), fatal events, TEAEs associated with treatment discontinuation, interruption, or reduction, and adverse events of special interest (AESIs) will be assessed.
From the time the informed consent form is signed up to 30 days after last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: Time from the date of first documented response (CR or PR) until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.
Time from the date of first documented response (CR or PR) until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: From baseline to date of first documented objective response of CR, up to approximately 56 months
Complete response rate is the percentage of participants achieving CR as the BOR based on BICR assessments.
From baseline to date of first documented objective response of CR, up to approximately 56 months
Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: Time from the date of first documented CR until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Duration of complete response is defined as the time from the date of the first documentation of CR to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.
Time from the date of first documented CR until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: From baseline to date of first documented objective response of PR, up to approximately 56 months
Partial response rate is the percentage of participants achieving PR as the BOR based on BICR assessment.
From baseline to date of first documented objective response of PR, up to approximately 56 months
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time Frame: From the time the informed consent form is signed up to 30 days after last dose
Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), severe events (Grades 3 and 4), fatal events, TEAEs associated with treatment discontinuation, interruption, or reduction, and adverse events of special interest (AESIs) will be assessed.
From the time the informed consent form is signed up to 30 days after last dose
Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy
Time Frame: Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 13 Day 1 Predose; Cycle 25 Day 1 Predose & every 3 cycles thereafter up to approximately 56 months (each cycle is 28 days)
Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma will be assessed.
Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 13 Day 1 Predose; Cycle 25 Day 1 Predose & every 3 cycles thereafter up to approximately 56 months (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daiichi Sankyo

Investigators

  • Study Director: Global Clinical Leader, Daiichi Sankyo

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 Major Dates

Study Start (Actual)

June 3, 2021

Primary Completion (Actual)

May 10, 2023

Study Completion (Estimated)

September 8, 2025

Study Registration Dates

First Submitted

January 7, 2021

First Submitted That Met QC Criteria

January 7, 2021

First Posted (Actual)

January 11, 2021

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DS3201-A-U202
  • 2020-004954-31 (EudraCT Number)
  • jRCT2071200095 (Other Identifier: JAPIC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. 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: https://vivli.org/ourmember/daiichi-sankyo/

IPD Sharing Time Frame

Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

IPD Sharing 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, the European Union and/or Japan 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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