Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
- Conditions
- Relapsed/Refractory Peripheral T-Cell LymphomaAdult T Cell Leukemia/Lymphoma
- Interventions
- Registration Number
- NCT04703192
- Lead Sponsor
- Daiichi Sankyo
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 155
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Written informed consent
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Participants ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
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Eastern Cooperative Oncology Group performance status of 0, 1, or 2
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Cohort 1 relapsed/refractory peripheral T-cell lymphoma (PTCL):
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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
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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.
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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
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Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy.
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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
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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.
Participants meeting any exclusion criteria for this study will be excluded from this study. Below is a list of the key exclusion criteria:
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Diagnosis of mycosis fungoides, Sézary syndrome and primary cutaneous ALCL, and systemic dissemination of primary cutaneous ALCL
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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
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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.
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Presence of active central nervous system involvement of lymphoma
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History of autologous HCT within 60 days prior to the first dose of study drug
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History of allogeneic HCT within 90 days prior to the first dose of study drug
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Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment
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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
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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
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History of treatment with other EZH inhibitors
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Current use of moderate or strong cytochrome P450 (CYP)3A inducers
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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.
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Known or suspected hypersensitivity to valemetostat tosylate or any of the excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma Valemetostat Tosylate 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. Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma Valemetostat Tosylate 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.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) From baseline to date of first documented objective response of CR, up to approximately 56 months Complete response rate is the percentage of participants achieving CR as the BOR based on BICR assessments.
Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy 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) Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma will be assessed.
Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) 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 (Cohort 1) From the time the informed consent form is signed up to 30 days after last dose Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) 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 Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR 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.
Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) 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 Duration of complete response is defined as the time from the date of the first documentation of CR 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.
Trial Locations
- Locations (60)
Weill Cornell Medicine
🇺🇸New York, New York, United States
City Of Hope National Medical Center
🇺🇸Duarte, California, United States
Stanford University Medical Center - Cancer Clinical Trials Office - ONCOLOGY
🇺🇸Palo Alto, California, United States
Emory University Hospital - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northwestern University - Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center at Memorial Hospital
🇺🇸New York, New York, United States
University of Pennsylvania Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Epworth Healthcare
🇦🇺Richmond, Australia
University Health Network Princess Margaret Hospital
🇨🇦Toronto, Canada
CHU de Dijon
🇫🇷Dijon, France
Centre Lyon Berard - Medical Oncology
🇫🇷Lyon, France
CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang
🇫🇷Lille, France
Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)
🇳🇱Leiden, Netherlands
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
BC Cancer - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Canada
APHP - Hopital Saint Louis
🇫🇷Paris, France
Hôpital Necker
🇫🇷Paris, France
Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)
🇫🇷Toulouse, France
Centre Hospitalier Lyon Sud - Hématologie
🇫🇷Pierre-Bénite, France
Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
🇩🇪Halle, Germany
PO San Gerardo, ASST Monza
🇮🇹Monza, Italy
A.O.di Bologna Policl.S.Orsola
🇮🇹Bologna, Italy
ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
🇮🇹Bergamo, Italy
Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
🇮🇹Napoli, 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, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Hokkaido University Hospital - Medical Oncology Center
🇯🇵Sapporo, Hokkaido, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
University Hospital - Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital - Department of Internal
🇰🇷Seoul, Korea, Republic of
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center - Hematology-Oncology
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
ICO Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
National Cheng Kung University Hospital - Internal Medicine
🇨🇳Tainan, Taiwan
National Taiwan University Hospital - Hematology And Oncology
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology
🇨🇳Taoyuan City, Taiwan
Churchill Hospital
🇬🇧Oxford, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Nottingham City Hospital - Clinical Haematology
🇬🇧Nottingham, United Kingdom
University Of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Hackensack University Medical Center - John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Universiteit Maastricht Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
🇨🇳Kaohsiung, Taiwan