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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04703192




Registration number
NCT04703192
Ethics application status
Date submitted
7/01/2021
Date registered
11/01/2021

Titles & IDs
Public title
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Scientific title
Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects With Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Secondary ID [1] 0 0
2020-004954-31
Secondary ID [2] 0 0
DS3201-A-U202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Peripheral T-Cell Lymphoma 0 0
Adult T Cell Leukemia/Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Valemetostat Tosylate

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.

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.


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [1] 0 0
From baseline until disease progression or death (whichever occurs first), up to approximately 23 months
Primary outcome [2] 0 0
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2)
Timepoint [2] 0 0
From the time the informed consent form is signed up to 30 days after last dose, up to 23 months
Secondary outcome [1] 0 0
Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy
Timepoint [1] 0 0
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 5 Day 1 Predose (each cycle is 28 days)
Secondary outcome [2] 0 0
Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [3] 0 0
From baseline to date of first documented objective response of CR, up to approximately 56 months
Secondary outcome [4] 0 0
Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [5] 0 0
From baseline to date of first documented objective response of PR, up to approximately 56 months
Secondary outcome [6] 0 0
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Timepoint [6] 0 0
From the time the informed consent form is signed up to 30 days after last dose

Eligibility
Key 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 ?d 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/09/2025
Actual
Sample size
Target
Accrual to date
Final
155
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Epworth Healthcare - Richmond
Recruitment postcode(s) [1] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
Canada
State/province [12] 0 0
British Columbia
Country [13] 0 0
Canada
State/province [13] 0 0
Ottawa
Country [14] 0 0
Canada
State/province [14] 0 0
Toronto
Country [15] 0 0
France
State/province [15] 0 0
Dijon
Country [16] 0 0
France
State/province [16] 0 0
Lille
Country [17] 0 0
France
State/province [17] 0 0
Lyon
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Pierre-Bénite
Country [20] 0 0
France
State/province [20] 0 0
Toulouse
Country [21] 0 0
Germany
State/province [21] 0 0
Halle
Country [22] 0 0
Italy
State/province [22] 0 0
Bergamo
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Monza
Country [25] 0 0
Italy
State/province [25] 0 0
Napoli
Country [26] 0 0
Italy
State/province [26] 0 0
Perugia
Country [27] 0 0
Japan
State/province [27] 0 0
Aichi
Country [28] 0 0
Japan
State/province [28] 0 0
Chiba
Country [29] 0 0
Japan
State/province [29] 0 0
Hokkaido
Country [30] 0 0
Japan
State/province [30] 0 0
Tokyo
Country [31] 0 0
Japan
State/province [31] 0 0
Fukuoka
Country [32] 0 0
Japan
State/province [32] 0 0
Kagoshima
Country [33] 0 0
Japan
State/province [33] 0 0
Kyoto
Country [34] 0 0
Japan
State/province [34] 0 0
Nagasaki
Country [35] 0 0
Japan
State/province [35] 0 0
Okayama
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul Teugbyeolsi
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Netherlands
State/province [38] 0 0
Leiden
Country [39] 0 0
Netherlands
State/province [39] 0 0
Maastricht
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Sevilla
Country [43] 0 0
Taiwan
State/province [43] 0 0
Kaohsiung
Country [44] 0 0
Taiwan
State/province [44] 0 0
Tainan
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taipei
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taoyuan City
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Nottingham
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04703192