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LymphomaPhase 1/2Epi-RCHOPNCT02889523

Study of Tazemetostat in Newly Diagnosed Diffuse Large B Cell and Follicular Lymphoma Patients Treated by Chemiotherapy

A Phase 1/2 study testing Tazemetostat, Rituximab and Cyclophosphamide in people with Lymphoma and DLBCL, run by The Lymphoma Academic Research Organisation at 31 sites in 2 countries.

Active, not recruiting

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

Official record
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Trial summary

Phase I of the study is designed to determine the recommended phase II dose (RP2D) for tazemetostat in patients treated with 8 cycles of R-CHOP 21. Phase II of the study is designed to determine the safety and the efficacy of tazemetostat in DLBCL and FL patients : DLBCL : tazemetostat with 6 cycles of R-CHOP 21 + 2… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Lymphoma, DLBCL, Follicular Lymphoma
What is being tested?
Tazemetostat, Rituximab and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
214 participants
Where
31 sitesin 2 countries
Study dates
Oct 2016to Sep 2029
Phase
Phase 1/2
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • for Cohort DLBCL ONLY
  • 1-Patients with an untreated DLBCL de novo or transformed from indolent lymphoma (CD 20 positive) with
  • Phase Ib aaIPI ≥ 2
  • Phase II: aaIPI ≥ 1ONLY
  • 2. Age between 60 and 80 years included
  • for Cohort FOLLICULAR ONLY
Show all 28Show fewer
  • 1-High Tumor Burden (as defined by GELF criteria > 0) frontline follicular lymphoma (FL) with high risk FLIPI 3-5
  • 2. Aged between 18 years and 80 years included
  • 11bis. Females of childbearing potential (FCBP) must agree to use one reliable form of contraception or to practice complete abstinence from heterosexual contact 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 12 months after discontinuation of any study treatments (R-CHOP, tazemetostat, Rituximab)
  • For both Cohorts
  • 1bis- For phase II patients: Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan and/or clinical examination AND a FDG avid disease by PETscan
  • 3.ECOG performance status of 0, 1 or 2 (0 or 1 only for phase Ib)
  • 4.Signed informed consent
  • 5.Life expectancy of ≥ 90 days (3 months) before starting tazemetostat
  • 6.Adequate renal function as calculated by a creatinine clearance > 40 mL/min by local institutional formula
  • 7. Adequate bone marrow function as defined as:
  • ANC ≥ 1500/mm3 (≥ 1.5 X 109/L)
  • Platelets ≥ 75,000/mm3 (≥ 75 X 109/L) without platelet transfusion dependency during the last 7 days
  • Hemoglobin ≥ 9 g/dL (may receive transfusion)
  • 8. Adequate liver function as defined as:
  • Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome
  • Alkaline phosphatase (in absence of bone disease), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 X ULN (or ≤ 5 X ULN if related to lymphoma involvement)
  • Patients with prior Hepatitis B and C are eligible if, for Hepatitis B detection, surface antigen is negative and/or HBV DNA is undetectable, and for Hepatitis C detection, if HCV RNA is undetectable.
  • 9. Left ventricular ejection fraction (LVEF) ≥ 50% of echocardiography or multiple gated acquisition (MUGA) scan
  • 10. Adequate tissue (surgical excision is recommended) for central pathology review and biological caracterisation (see appendix 11
  • 11. Males with partners of childbearing potential must agree to use reliable forms of contraception during 12 months after last treatment administration
  • 12. Patient covered by any social security system (for France only)
  • 13. Patient who understands and speaks one of the country official languages

Who cannot join

  • for Cohort DLBCL
  • 15-Previous treatment for B cell lymphoma, except glucocorticoids (no more than 7 days before inclusion, 1 mg/kg/day max)
  • for Cohort FOLLICULAR ONLY
  • 14bis. Prior therapy for lymphoma including radiotherapy except glucocorticoids (no more than 7 days before inclusion, 1 mg/kg/day max)
  • 17-Pregnant or lactating females
  • For both Cohorts
Show all 25Show fewer
  • 1-Central nervous system or meningeal involvement
  • 2-Contraindication to any drug contained in the chemotherapy regimen
  • 3-Prior treatment with tazemetostat or other inhibitor of EZH2
  • 4-Patients who are undergoing active treatment for another malignancy, exceptions include: A patient who has been disease free for 2 years, or a patient with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible Patients with prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia(AML) or prior history of T-LBL/T-ALL are excluded whatever receiving treatment or not and whatever date of diagnosis of these pathologies
  • 5-Patients taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's wort)
  • 6-Patients unwilling to exclude St. John's wort, Seville oranges, grapefruit juice and/or grapefruit from diet
  • 7-Major surgery within 4 weeks before first dose of study drug (minor procedures including transcutaneous biopsy, central line placement are permitted within 2 weeks of enrollment)
  • 8-Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition that would impare ability to take tazemetostat
  • 9-Significant cardiovascular impairment: congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of first dose of tazemetostat or ventricular arrhythmia
  • 10-Not applicable
  • 11-Active uncontrolled infection requiring systemic therapy
  • 12-Congenital immunodeficiency or known HIV (human immunodeficiency virus infection)
  • 13-Any other major illness, that in the investigator's judgement, will substantially increase the risk associated with the patient's participation in the study
  • 14-Patients who have undergone a solid organ transplant
  • 16-Treatment with any investigational drug or device within 30 days before planned first cycle of chemotherapy
  • 18-Person deprived of his/her liberty by a judicial or administrative decision
  • 19-Adult person under legal protection
  • 20-Person hospitalized without consent
  • 21-Adult person unabled to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

France28 sites

  • Centre Hospitalier Victor Dupouy

    Argenteuil

  • CH d'Avignon - Hôpital Henri Dufaut

    Avignon

  • CHU de Besançon - Hôpital Jean Minjoz

    Besançon

  • Polyclinique Bordeaux Nord Aquitaine

    Bordeaux

  • CH de Chambéry

    Chambéry

  • CHU d'Estaing

    Clermont-Ferrand, France

  • APHP - Hopital Henri Mondor

    Créteil

  • CHU de Dijon

    Dijon

  • CHU Grenoble

    Grenoble

  • CH Départemental de Vendée

    La Roche-sur-Yon

  • CHRU Lille - Hôpital Claude Huriez

    Lille

  • Chu de Limoges - Hopital Dupuytren

    Limoges

  • Centre Leon Berard

    Lyon

  • Institut Paoli Calmette

    Marseille

  • CHU de Montpellier - Hôpital Saint-Eloi

    Montpellier

  • CHU de Nantes - Hôtel Dieu

    Nantes

  • APHP - Hôpital de la Pitié Salpetrière

    Paris

  • APHP - Hôpital Saint Louis

    Paris

  • CH de Perpigan

    Perpignan

  • CHU Lyon Sud

    Pierre-Bénite

  • Chu de Poitiers - Hopital de Miletrie

    Poitiers

  • CHU de Rennes - Hôpital Pontchaillou

    Rennes

  • Centre Henri Becquerel

    Rouen, 76000

  • Centre Rene Hugenin

    Saint-Cloud

  • Institut de cancérologie de la Loire

    Saint-Priest-en-Jarez

  • CHRU de Strasbourg

    Strasbourg

  • Institut Universitaire du Cancer de Toulouse - Oncopole

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Belgium3 sites

  • Institut Jules Bordet

    Brussels

  • CHU de Liege

    Liège

  • CHRU Mont Godinne

    Yvoir

Other trials in Belgium

About this study

Official title: A Phase Ib-II Study of Tazemetostat (EPZ-6438) in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) or High Risk Follicular Lymphoma (FL) Patients Treated by R-CHOP

Phase I of the study is designed to determine the recommended phase II dose (RP2D) for tazemetostat in patients treated with 8 cycles of R-CHOP 21.

Phase II of the study is designed to determine the safety and the efficacy of tazemetostat in DLBCL and FL patients :

DLBCL : tazemetostat with 6 cycles of R-CHOP 21 + 2 cycles of Rituximab FL : tazemetostat with 6 cycles of R-CHOP 21 + 2 cycles of Rituximab then maintenance with 6 months of tazemetostat and 24 months of Rituximab

Read the detailed description

Phase I:

Up to 18 patients will be recruited, using a conventional dose-escalation algorithm (3+3 patients per dose level) to identify the maximum tolerated dose (MTD) which will be deemed the RP2D. Patients will receive 8 cycles of RCHOP every 21 days and tazemetostat every day, starting on day 2 of cycle 1.

4 cohorts are defined, according to dose levels of tazemetostat: 400mg Twice a day (BID) (cohort 1, starting level), 600mg BID (cohort 2), 800mg BID (cohort 3), 200mg BID (cohort -1), depending on the observed toxicities.

Phase II:

Up to 184 patients (122 DLBCL and 62 FL) will be recruited and treated with tazemetostat at the MTD and RCHOP.

Patients will receive 6 cycles of RCHOP every 21 days and tazemetostat at the MTD every day, starting on day 2 of cyle 1, + 2 cycles of Rituximab+tazemetostat. For FL, a maintenance of tazemetostat (6 months) + rituximab (24 months) is expected

Being tested
Tazemetostat, Rituximab, Cyclophosphamide, Vincristine, Doxorubicin
Keywords
Front line therapy, Age-adjusted International Prognostic Index (aa-IPI) >1, 60 to 80 years
Medical subject headings
Lymphoma, Lymphoma, Follicular

What participants receive

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

  • TazemetostatDrug

    Also called EPZ-6438

    Tablets 200 mg, to be administrated per os

  • RituximabDrug

    Also called Mabthera

    375 mg/m²/dose, D1

  • CyclophosphamideDrug

    750 mg/m²/dose, D1

  • VincristineDrug

    1.4 mg/m²/dose (max 2 mg), D1

  • DoxorubicinDrug

    50 mg/m²/dose, D1

  • PrednisoloneDrug

    40 mg/m2 in the morning D1 to D5

Study groups in NCT02889523
Study groupRoleWhat they receive
DLBCL cohortExperimentalRCHOP + tazemetostat: - RCHOP: rituximab (IV, 375 mg/m², day 1), Prednisolone (PO, 40 mg/m² in the morning, day 1 to day 5), doxorubicine (IV, 50 mg/m², day 1), cyclophosphamide (IV, 750 mg/m², day 1), vincristine (IV, 1.4 mg/m², day 1): Phase I : 8 cycles, every 21 days Phase II : 6 cycles, every 21 days * Rituximab (IV, 375 mg/m², day 1) Phase II : 2 cycles, every 21 days * Tazemetostat: PO, doses according to dose cohorts for phase I, and at RP2D for phase II: continuous: Cycle 1: 2 to 21 BID, Cycle 2-8: 1 to 21 BID
Receives: Drug: Tazemetostat; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisolone
FL cohortExperimentalRCHOP + tazemetostat: Induction * RCHOP: rituximab (IV, 375 mg/m², day 1), Prednisolone (PO, 40 mg/m² in the morning, day 1 to day 5), doxorubicine (IV, 50 mg/m², day 1), cyclophosphamide (IV, 750 mg/m², day 1), vincristine (IV, 1.4 mg/m², day 1): 6 cycles, every 21 days * Rituximab (IV, 375 mg/m², day 1) Phase II : 2 cycles, every 21 days * Tazemetostat: PO, RP2D, continuous: Cycle 1: 2 to 21 BID, Cycle 2-8: 1 to 21 BID Maintenance * Tazemetostat : 6 months (every 8 weeks) * Rituximab : 24 months (every 8 weeks)
Receives: Drug: Tazemetostat; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisolone

What is being measured

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

  1. Phase I : Number of Dose Limiting Toxicities

    Incidence and severity of treatment-emergent AEs qualifying as protocol defined DLT's in cycle 1 and 2 in order to establish the MTD/RP2D

    Measured: 1 cycle (1 cycle is 21 days)

  2. Phase I : Number of Dose Limiting Toxicities

    Incidence and severity of treatment-emergent AEs qualifying as protocol defined DLT's in cycle 1 and 2 in order to establish the MTD/RP2D

    Measured: 2 cycles (1 cycle is 21 days)

  3. Phase II - DLBCL Cohort : Complete Response Rate based on local assessment

    Complete response rate as determined by Cheson International Work Group (IWG) 2014: Lugano Classification (Deauville scale 1-3)

    Measured: 8 cycles (1 cycle is 21 days)

  4. Phase II - FL Cohort : Complete Response Rate based on local assessment

    Complete response rate as determined by Cheson IWG 2014: Lugano Classification (Deauville scale 1-3)

    Measured: 8 cycles (1 cycle is 21 days)

Secondary outcomes (25)

  1. Phase I : Serum concentration of CHOP components in presence/absence of Tazemetostat

    Measured: Change between baseline - 1 month

  2. Phase I : Serum concentration of Tazemetostat and its metabolite (EZH 6930) in presence of CHOP

    Measured: Change between baseline - 1 month

  3. Phase I : Complete response rate (CRR) by central review using Cheson IWG criteria

    Measured: 8 cycles (1 cycle is 21 days)

  4. Phase II - DLBCL Cohort : Number of Adverse Events (AE)/Serious Adverse Events (SAE)

    Measured: 8 cycles (1 cycle is 21 days)

  5. Phase II - DLBCL Cohort : Complete response rate (CRR) by central review using Cheson IWG criteria

    Measured: 8 cycles (1 cycle is 21 days)

  6. Phase II - DLBCL Cohort : Overall response rate (ORR) by central review

    Measured: 52 weeks

  7. Phase II - DLBCL Cohort : Overall response rate (ORR) by central review

    Measured: 104 weeks

  8. Phase II - DLBCL Cohort : progression free survival (PFS)

    Measured: 52 weeks

  9. Phase II - DLBCL Cohort : progression free survival (PFS)

    Measured: 104 weeks

  10. Phase II - DLBCL Cohort : duration of response (DR)

    Measured: 52 weeks

  11. Phase II - DLBCL Cohort : duration of response (DR)

    Measured: 104 weeks

  12. Phase II - DLBCL Cohort : overall survival (OS)

    Measured: 52 weeks

  13. Phase II - DLBCL Cohort : overall survival (OS)

    Measured: 104 weeks

  14. Phase II - DLBCL Cohort : best overall response (BOR)

    Measured: 104 weeks

  15. Phase II - FL cohort : Number of AE/SAE

    Measured: 8 cycles (1 cycle is 21 days)

  16. Phase II - FL cohort : Number of AE/SAE

    Measured: 13 months

  17. Phase II - FL cohort : PET Complete Response Rate (PET-CRR) by central review according to Lugano 2014 criteria

    Measured: 8 cycles (1 cycle is 21 days)

  18. Phase II - FL cohort : Complete Response Rate (CRR)

    Measured: 31 months

  19. Phase II - FL cohort : Overall Response Rate (CRR)

    Measured: 31 months

  20. Phase II - FL cohort : Progression Free Survival (PFS)

    Measured: 24 months

  21. Phase II - FL cohort : Progression Free Survival (PFS)

    Measured: 31 months

  22. Phase II - FL cohort : Event Free Survival (EFS)

    Measured: 24 months

  23. Phase II - FL cohort : Overall Survival (OS)

    Measured: 24 months

  24. Phase II - FL cohort : Duration of Response (DR)

    Measured: 31 months

  25. Phase II - FL cohort : Best Overall Response

    Measured: 31 months

Timeline

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

  1. First posted5 Sep 2016 (estimated)
  2. Study startOct 2016
  3. Primary completion31 Jan 2023
  4. Study completionSep 2029 (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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
214 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02889523
Sponsor's protocol ID
Epi-RCHOP
Acronym
Epi-RCHOP
Status last verified
Jul 2026
First submitted
11 Jul 2016
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Sarkozy C, Morschhauser F, Dubois S, Molina T, Michot JM, Cullieres-Dartigues P, Suttle B, Karlin L, Le Gouill S, Picquenot JM, Dubois R, Tilly H, Herbaux C, Jardin F, Salles G, Ribrag V. A LYSA Phase Ib Study of Tazemetostat (EPZ-6438) plus R-CHOP in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) with Poor Prognosis Features. Clin Cancer Res. 2020 Jul 1;26(13):3145-3153. doi: 10.1158/1078-0432.CCR-19-3741. Epub 2020 Mar 2.

    PubMed 32122924

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tazemetostat, Rituximab and Cyclophosphamide in people with Lymphoma and DLBCL, run by The Lymphoma Academic Research Organisation at 31 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 28 inclusion and 25 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 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Phase I : Number of Dose Limiting Toxicities (time frame: 1 cycle (1 cycle is 21 days)). The study lists 4 primary outcomes in all. 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 NCT02889523, which also lists 1 linked publication.

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 11 Aug 2026.

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