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
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) — From baseline until disease progression or death (whichever occurs first), up to approximately 23 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.
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2) — From the time the informed consent form is signed up to 30 days after last dose, up to 23 months Treatment-emergent adverse events (TEAEs) were defined as new AEs or pre-existing conditions that worsen in National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade after the first dose of study drug and up to 30 days after the last dose of study drug.
Trial sites (60)
Facility
City
Region
Status
City Of Hope National Medical Center
Duarte
California
Stanford University Medical Center - Cancer Clinical Trials Office - ONCOLOGY
Palo Alto
California
University of California San Francisco
San Francisco
California
University Of Colorado Cancer Center
Aurora
Colorado
Emory University Hospital - Winship Cancer Institute
Atlanta
Georgia
Northwestern University - Feinberg School of Medicine
Chicago
Illinois
Dana Farber Cancer Institute
Boston
Massachusetts
Mayo Clinic - Rochester
Rochester
Minnesota
Washington University School of Medicine
St Louis
Missouri
Hackensack University Medical Center - John Theurer Cancer Center
Hackensack
New Jersey
Memorial Sloan-Kettering Cancer Center at Memorial Hospital
New York
New York
Weill Cornell Medicine
New York
New York
Duke Cancer Center
Durham
North Carolina
University of Pennsylvania Perelman Center for Advanced Medicine
Philadelphia
Pennsylvania
Epworth Healthcare
Richmond
Australia
BC Cancer - Vancouver Centre
Vancouver
British Columbia
Ottawa Hospital Research Institute
Ottawa
Canada
University Health Network Princess Margaret Hospital
Toronto
Canada
CHU de Dijon
Dijon
France
CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang
Lille
France
Centre Lyon Berard - Medical Oncology
Lyon
France
APHP - Hopital Saint Louis
Paris
France
Hôpital Necker
Paris
France
Centre Hospitalier Lyon Sud - Hématologie
Pierre-Bénite
France
Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)
Toulouse
France
Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
Halle
Germany
ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
Bergamo
Italy
A.O.di Bologna Policl.S.Orsola
Bologna
Italy
PO San Gerardo, ASST Monza
Monza
Italy
Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
Naples
Italy
Ospedale S.Maria della Misericordia, AO di Perugia, Università degli Studi di Perugia
Perugia
Italy
National Hospital Organization Nagoya Medical Center - Hematology
Nagoya
Aichi-ken
Nagoya City University Hospital
Nagoya
Aichi-ken
National Cancer Center Hospital East
Kashiwa
Chiba
Hokkaido University Hospital - Medical Oncology Center
Sapporo
Hokkaido
National Cancer Center Hospital
Chuo Ku
Tokyo
Kyushu University Hospital
Fukuoka
Japan
Kagoshima University Hospital
Kagoshima
Japan
University Hospital - Kyoto Prefectural University of Medicine
Kyoto
Japan
Nagasaki University Hospital
Nagasaki
Japan
+ 20 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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