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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)

NCT04703192

Description:

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.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Follicular T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: DS3201-A-U202
  • SECONDARY ID: 2020-004954-31
  • SECONDARY ID: jRCT2071200095
  • NCT ID: NCT04703192

Conditions

  • Relapsed/Refractory Peripheral T-Cell Lymphoma
  • Adult T Cell Leukemia/Lymphoma

Interventions

DrugSynonymsArms
Valemetostat TosylateDS-3201bCohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Relapsed/Refractory Peripheral T-Cell LymphomaExperimentalParticipants 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.
  • Valemetostat Tosylate
Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/LymphomaExperimentalParticipants 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.
  • Valemetostat Tosylate

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Complete response rate is the percentage of participants achieving CR (and CRu [ATL only]) as the BOR based on BICR assessments.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Partial response rate is the percentage of participants achieving PR as the BOR based on BICR assessment.
Measure: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
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Relapsed/Refractory Peripheral T-Cell Lymphoma
  • Adult T-Cell Leukemia/Lymphoma
  • Valemetostat Tosylate
  • DS-3201b

Last Updated

July 13, 2021