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

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ClinicalTrials.gov Identifier: NCT04703192
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE January 7, 2021
First Posted Date  ICMJE January 11, 2021
Last Update Posted Date January 5, 2022
Actual Study Start Date  ICMJE June 3, 2021
Estimated Primary Completion Date December 3, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2021)
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy [ 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. For the adult T-cell leukemia/lymphoma cohort, ORR is defined as the proportion of participants with a BOR of CR, uncertified CR (CRu), or PR, assessed by BICR, among participants with centrally confirmed histology/peripheral blood assessment.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy [ 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. For the adult T-cell leukemia/lymphoma cohort, ORR is defined as the proportion of participants with a BOR of CR, uncertified CR (CRu), or PR, assessed by BICR, among participants with positive anti-HTLV-1 antibody.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
  • Duration of Response After Administration of Valemetostat Tosylate Monotherapy [ Time Frame: Time from the date of first documented response (CR, CRu [ATL only], 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, CRu [ATL only], 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.
  • Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy [ Time Frame: From baseline to date of first documented objective response of CR (CRu [ATL only]), up to approximately 56 months ]
    Complete response rate is the percentage of participants achieving CR (and CRu [ATL only]) as the BOR based on BICR assessments.
  • Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy [ Time Frame: Time from the date of first documented CR (also CRu [ATL only]) 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 (also CRu [ATL only]) 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.
  • Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy [ 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.
  • Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy [ 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Official Title  ICMJE Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects With Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Brief Summary 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.
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, including relapsed/refractory adult T-cell leukemia/lymphoma participants.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed/Refractory Peripheral T-Cell Lymphoma
  • Adult T Cell Leukemia/Lymphoma
Intervention  ICMJE 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 Name: DS-3201b
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Valemetostat Tosylate
  • 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.
    Intervention: Drug: Valemetostat Tosylate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2021)
176
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2026
Estimated Primary Completion Date December 3, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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):

    • Should be pathologically confirmed by the local pathologist/investigators; 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 pathologically or hematocytologically confirmed by the local pathologist/investigators; local histological/hematocytological 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 lymphoblastic 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 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 or right 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: (US sites) Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com
Contact: (Asia sites) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111(M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp
Listed Location Countries  ICMJE Australia,   Canada,   France,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04703192
Other Study ID Numbers  ICMJE DS3201-A-U202
2020-004954-31 ( EudraCT Number )
jRCT2071200095 ( Other Identifier: JAPIC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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 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/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP