Clinical trial NCT04703192: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed/Refractory Peripheral T-Cell Lymphoma
Adult T Cell Leukemia/Lymphoma
Keywords: Relapsed/Refractory Peripheral T-Cell Lymphoma
Adult T-Cell Leukemia/Lymphoma
Valemetostat Tosylate
DS-3201b
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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):

  * 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

Primary outcomes:
measure: Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: From baseline until disease progression or death (whichever occurs first), up to approximately 23 months
measure: Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2)
timeFrame: From the time the informed consent form is signed up to 30 days after last dose, up to 23 months
Secondary outcomes:
measure: Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy
timeFrame: 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)
measure: Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: 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
measure: Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: From baseline to date of first documented objective response of CR, up to approximately 56 months
measure: Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: 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
measure: Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: From baseline to date of first documented objective response of PR, up to approximately 56 months
measure: Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
timeFrame: From the time the informed consent form is signed up to 30 days after last dose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City Of Hope National Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center - Cancer Clinical Trials Office - ONCOLOGY
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University Of Colorado Cancer Center
state: Colorado
city: Atlanta
country: United States
facility: Emory University Hospital - Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center - John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center at Memorial Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Perelman Center for Advanced Medicine
state: Pennsylvania
city: Richmond
country: Australia
facility: Epworth Healthcare
city: Vancouver
country: Canada
facility: BC Cancer - Vancouver Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
city: Toronto
country: Canada
facility: University Health Network Princess Margaret Hospital
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang
city: Lyon
country: France
facility: Centre Lyon Berard - Medical Oncology
city: Paris
country: France
facility: APHP - Hopital Saint Louis
city: Paris
country: France
facility: Hôpital Necker
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud - Hématologie
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
city: Bologna
country: Italy
facility: A.O.di Bologna Policl.S.Orsola
city: Monza
country: Italy
facility: PO San Gerardo, ASST Monza
city: Napoli
country: Italy
facility: Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
city: Perugia
country: Italy
facility: Ospedale S.Maria della Misericordia, AO di Perugia, Università degli Studi di Perugia
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center - Hematology
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo
country: Japan
facility: Hokkaido University Hospital - Medical Oncology Center
state: Hokkaido
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kyoto
country: Japan
facility: University Hospital - Kyoto Prefectural University of Medicine
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital - Department of Internal
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - Hematology-Oncology
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)
city: Maastricht
country: Netherlands
facility: Universiteit Maastricht Academisch Ziekenhuis Maastricht
city: Barcelona
country: Spain
facility: ICO Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital - Internal Medicine
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital - Hematology And Oncology
city: Taoyuan City
country: Taiwan
facility: Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology
city: London
country: United Kingdom
facility: University College London Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital - Clinical Haematology
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: