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Lymphoma, B-CellPhase 2NCT04842877

Study of Valemetostat Tosylate as a Single Agent in Patients With Relapse/Refractory B-cell Lymphoma

A Phase 2 study testing Valemetostat tosylate in people with Lymphoma, B-Cell, run by The Lymphoma Academic Research Organisation at 22 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a multicenter, prospective, single arm, non-randomized, open-label, phase 2 clinical study to evaluate safety and efficacy of valemetostat tosylate (DS-3201b) in patients with relapsed or refractory B cell lymphoma with 6 cohorts of patients including 2 biology-driven cohorts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
Valemetostat tosylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
22 sitesin 2 countries
Study dates
11 Jun 2021to Oct 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1 - Participants with confirmed histological diagnosis of B-cell non-Hodgkin's lymphoma of aggressive B-cell lymphoma (diffuse large B-cell lymphoma-not otherwise specified, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma-not otherwise specified and high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, transformed indolent lymphoma and grade 3b follicular lymphoma), FL (grade 1, 2, 3a), MCL, MZL or other indolent lymphoma (Waldenström macroglobulinemia), or HL according to the World Health Organization (WHO) 2016 classification of hematopoietic and lymphoid tissue.
  • 2. Participant who had progressive disease (PD) or did not have a response (CR or PR) in previous systemic therapy, or relapsed or progressed after previous systemic therapy 3. Participant who has measurable disease by the Lugano criteria (ie longest diameter of a nodal site > 1.5cm and/or longest diameter of an extranodal site > 1.0 cm) 4. Participant who had previous standard therapy with at least: (note: patients having received prior CAR-T therapy can be enrolled):
  • For aggressive B-cell lymphoma : 1 prior line of therapy (in transformed indolent lymphoma patient must have received at least one line of treatment containing an anthracycline-based regimen before of after transformation) containing an anti-CD20 antibody and an anthracycline (unless anthracycline-based therapy is contraindicated) and if patient is considered unable to benefit from intensification treatment with autologous stem cell transplant (ASCT) as defined by at least one of the following criteria:
  • Relapsed following, or refractory to, previous ASCT
  • Ineligible for intensification treatment due to age or significant comorbidity
  • Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
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  • Refused intensification treatment and/or ASCT
  • For FL, MZL and other indolent non-Hodgkin's lymphoma (NHL): 2 prior lines of systemic therapy with at least one anti-CD20 monoclonal antibody. Local involved field radiotherapy for limited stage disease is not considered as a previous line. Subjects with prior ASCT may be included. Note: for Splenic Marginal Zone Lymphoma (SMZL), splenectomy is considered as one line; for Extranodal Marginal Zone Lymphoma (ENMZL), Helicobacter pylori eradication is not considered as a previous line.
  • For MCL: 2 prior lines including at least one immunochemotherapy and one BTK inhibitor.
  • For HL: 3 prior lines including at least one line with anthracycline-based chemotherapy (unless anthracycline-based therapy is contraindicated), one line containing brentuximab-vedotin and one line containing an anti-PD1 or anti-PDL1 antibody and must be considered unable to benefit from intensification treatment with autologous stem cell transplant (ASCT) as defined by at least one of the following criteria:
  • Relapsed following, or refractory to, previous ASCT
  • Did not achieve at least a partial response to a standard salvage regimen
  • Ineligible for intensification treatment due to age or significant comorbidity
  • Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
  • Refused intensification treatment and/or ASCT 5. Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. Adequate renal function defined as calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula 7. Adequate bone marrow function:
  • Absolute neutrophil count (ANC) > 1000/mm3 (≥ 1 × 109/L) without growth factor support (G-CSF) for at least 7 days
  • Platelets ≥ 75,000/mm3 (≥ 75 × 109/L) evaluated after at least 7 days since last platelet transfusion
  • Hemoglobin > 8.0 g/dL evaluated after at least 7 days since last transfusion 8. Adequate liver function:
  • Total bilirubin < 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia due to Gilbert's syndrome
  • Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) < 3 × ULN (< 5 × ULN if subject has liver involvement due to lymphoma) 9. Adequate tissue (surgical excision is recommended) for central pathology review and biological characterisation 10. Patient being successfully tested for EZH2 mutation status at study specific laboratories (for cohort 1, 2 and 2bis) 11. Subjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and have undetectable serum hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA, respectively.
  • 12. Females of childbearing potential must agree to use an highly effective birth control methods (defined in §13.6.1) during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 3 months after discontinuation of study treatment 13. Males with partners of childbearing potential must agree to use highly effective birth control methods during the study and 3 months after last treatment administration 14. Male and female participant ≥18 years of age at the time of informed consent 15. Patient covered by any social security system (France) 16. Patient who understands and speaks one of the country official language 17. Participant who has provided written consent to participate in the study

Who cannot join

  • Participant with prior exposure to EZH2 inhibitor
  • Participant with active lymphomatous involvement of the central nervous system (CNS) at screening
  • Any prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy), clinically significant toxicities have not resolved to ≤ Grade 1 per CTCAE version 5.0, or prior treatment-related toxicities are clinically unstable and clinically significant at time of enrollment.
  • Major surgery within 4 weeks before the first dose of study drug.
  • Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of the drug
  • Subjects currently taking medications that are known moderate or strong CYP3A inducers
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  • If currently used, these medications need to be discontinued at least 14 days prior to study drug administration; replacement by alternative medications that are not moderate or strong CYP3A inducers can be considered according to medical need
  • Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine)
  • Use of any standard or experimental anti-cancer drug therapy within 4 weeks or a minimum of 3 half lives of the drug, whatever the shortest prior to first administration of study drug,
  • History of CAR T-cells therapy within 30 days prior to the first dose of study drug
  • History of autologous or allogeneic hematopoietic cell transplantation (HCT) within 90 days prior to the first dose of study drug
  • Patients taking corticosteroids within 2 weeks prior to first administration of study drug, unless administered at a cumulated dose equivalent of prednisone to ≤ 10mg /day (within these 2 weeks).
  • Participant with significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia
  • Subjects with malignancies other than B cell lymphomas except subjects who have been disease-free for 2 years (subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible).
  • Positive serology of human immunodeficiency virus (HIV)
  • Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 470 milliseconds (msec) (obtained on average of 3 ECGs)
  • Participant with venous thrombosis or pulmonary embolism not treated
  • Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis
  • Participant with active infection requiring systemic therapy
  • Woman who are pregnant (positive serum pregnancy test at screening) or breastfeeding
  • Participant who were deemed as inappropriate to participate in the study by the investigator or coinvestigator

Trial locations and contacts

22 sites in 2 countries.

22 sites in 2 countries

France18 sites

  • CH d'Avignon

    Avignon, 84000

  • CH de la Côte Basque

    Bayonne, 64109

  • Institut Bergonié

    Bordeaux, 33076

  • Institut d'Hématologie de Basse Normandie

    Caen, 14076

  • Ch Metropole Savoie - Site Chambery

    Chambéry, 73000

  • CHU d'Estaing

    Clermont-Ferrand, 63000

  • François Lemonnier

    Créteil, 94010

  • CHU de Dijon

    Dijon, 21034

  • Chd de Vendee

    La Roche-sur-Yon, 85925

  • Clinique Victor Hugo

    Le Mans, 72000

  • Service des Maladies du Sang - CHRU de Lille

    Lille, 59037

  • Institut Paoli Calmette

    Marseille, 13273

  • CHU de Montpellier

    Montpellier, 34295

  • Gh Region Mulhouse Et Sud Alsace

    Mulhouse, 68070

  • CHU Hôtel Dieu

    Nantes, 44093

  • Emmanuel Bachy

    Pierre-Bénite, 69495

  • CHU Pontchaillou

    Rennes, 35003

  • Ch de Bretagne Atlantique -

    Vannes, 56017

Other trials in France

Belgium4 sites

  • A.Z. Sint Jan AV

    Bruges, 8000

  • University Hospital Gent

    Ghent, 9000

  • CH Tourelle Peltzer

    Verviers, 4800

  • CHU Mont-Godinne

    Yvoir

Other trials in Belgium

About this study

Official title: A Phase II Open-label Study Evaluating Valemetostat Tosylate as a Single Agent in Patients With Relapse/Refractory B-cell Lymphoma

This is a multicenter, prospective, single arm, non-randomized, open-label, phase 2 clinical study to evaluate safety and efficacy of valemetostat tosylate (DS-3201b) in patients with relapsed or refractory B cell lymphoma with 6 cohorts of patients including 2 biology-driven cohorts. Up to 141 patients will be enrolled in 6 different cohorts (40 patients with aggressive B-cell lymphoma, 41 with follicular lymphoma (FL), 20 with Mantle Cell Lymphoma (MCL) and 20 with other indolent lymphomas, and 20 patients with Hodgkin lymphoma (HL)). FL patients with EZH2 mutant (gain of function mutations) will be enrolled in the cohort 2bis. At least 8 aggressive B-cell lymphoma patients with EZH2 mutant will be enrolled in the cohort 1. The primary endpoint is the overall response rate (ORR) determined by investigator assessment.

Read the detailed description

Each cycle consists of 28 days. Valemetostat tosylate (DS-3201b) is given continuously at 200 mg once daily (QD). The total duration is expected to be approximately 3 years, assuming an expected enrollment duration of 2 years and a minimum duration of valemetostat tosylate (DS- 3201b) administration of 12 cycles of 28 days for the last enrolled patient.

Being tested
Valemetostat tosylate
Keywords
relapse, valemetostat tosylate
Medical subject headings
Lymphoma, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Valemetostat tosylateDrug

    Also called DS-3201b

    200mg QD continuously until disease progression, consent withdrawal, unacceptable drug-related toxicity, lost to follow-up, major protocol deviation, pregnancy, termination by sponsor or death, whichever occurs first.

Study groups in NCT04842877
Study groupRoleWhat they receive
Experimental armExperimentalExperimental arm: Valemetostat tosylate (DS-3201b) is given continuously at 200 mg QD.
Receives: Drug: Valemetostat tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR according to Lugano Response Criteria (2014)

    Measured: when mature response rate data have been observed, estimated as no later than 12 months after the last patient in each cohort has received the first dose of study drug

Secondary outcomes (16)

  1. Complete Response Rate (CRR)

    CRR according to Lugano response Criteria

    Measured: After 3 cycles of treatment (each cycle of 28 days, id est (ie) 3 months)

  2. Complete Response (CR) Rate

    CRR according to Lugano response Criteria

    Measured: After 6 cycles of treatment (each cycle of 28 days, id est (ie) 6 months)

  3. Complete Response (CR) Rate

    CRR according to Lugano response Criteria

    Measured: After 9 cycles of treatment (each cycle of 28 days, id est (ie) 9 months)

  4. Complete Response (CR) Rate

    CRR according to Lugano response Criteria

    Measured: After 12 cycles of treatment (each cycle of 28 days, id est (ie) 12 months)

  5. Progression-Free Survival (PFS)

    PFS is defined as the time from inclusion into the study to the first observation of documented clinical disease progression or death due to any cause.

    Measured: After 12 cycles(each cycle is 28 days) of study treatment for the last patient included (estimated 3 years of study)

  6. Duration of response (DoR)

    The DoR is defined as the time from attainment of CR or PR based on Lugano Response Criteria 2014 to the date of first documented disease progression, relapse (local assessment) or death from any cause

    Measured: After 12 cycles (each cycle is 28 days) of study treatment for the last patient included (estimated 3 years of study)

  7. Time to Response (TTR)

    The TTR is defined defined as the time from the first dose date to the date of attainment of CR or PR based on Lugano Response Criteria 2014

    Measured: After 12 cycles (each cycle is 28 days) of study treatment for the last patient included (estimated 3 years of study)

  8. Number of Serious Adverse Events (SAE)

    The frequency of SAE

    Measured: After 12 cycles of study treatment (each cycle is 28 days) for the last patient included (estimated 3 years of study)

  9. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: predose

  10. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: 1 hour post-dose at Cycle1 Day 1

  11. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: 2 hours post-dose at Cycle1 Day 1

  12. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: 4 hours post-dose at Cycle1 Day 1

  13. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: 5 hours post-dose at Cycle1 Day 1

  14. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: predose at Cycle1 Day 8

  15. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: predose at Cycle1 Day 15

  16. Pharmacokinetics: quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    quantity of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a)

    Measured: predose at Cycle1 Day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2021
  2. Study start11 Jun 2021
  3. Primary completion3 Dec 2024
  4. Study completionOct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a multicenter, prospective, single arm, non-randomized, open-label, phase 2 clinical study
Masking
None (open label)
Enrolment
141 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04842877
Sponsor's protocol ID
VALYM
Status last verified
Feb 2026
First submitted
7 Apr 2021
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Valemetostat tosylate in people with Lymphoma, B-Cell, run by The Lymphoma Academic Research Organisation at 22 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: when mature response rate data have been observed, estimated as no later than 12 months after the last patient in each cohort has received the first dose of study drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04842877.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.

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