We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Tazemetostat in Newly Diagnosed Diffuse Large B Cell Lymphoma Patients Treated by Chemiotherapy (Epi-RCHOP)

This study is currently recruiting participants.
Verified July 2017 by The Lymphoma Academic Research Organisation
Sponsor:
ClinicalTrials.gov Identifier:
NCT02889523
First Posted: September 5, 2016
Last Update Posted: July 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Epizyme, Inc.
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
  Purpose

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

Phase II of the study is designed to determine the safety of tazemetostat in patients treated with 8 cycles of R-CHOP 21 and to determine the complete response rate according to Cheson International Working Group (IWG) 2014: Lugano Classification (i.e. Deauville scale 1-3) after 8 cycles of Epi-RCHOP 21.


Condition Intervention Phase
Lymphoma, Large B-Cell, Diffuse Drug: Tazemetostat Drug: Rituximab Drug: Cyclophosphamide Drug: Vincristine Drug: Doxorubicin Drug: Prednisolone Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib-II Study of Tazemetostat (EPZ-6438) in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients With Poor Prognosis Treated by Rituximab-Cyclophosphamide-Vincristine-Doxorubicin-Prednisolone Chemiotherapy (R-CHOP)

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • Phase I : Number of Dose Limiting Toxicities [ Time Frame: 1 cycle (1 cycle is 21 days) ]
    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

  • Phase I : Number of Dose Limiting Toxicities [ Time Frame: 2 cycles (1 cycle is 21 days) ]
    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

  • Phase II : Number of Serious Adverse Events (SAE) et Adverse Events (AE) [ Time Frame: 8 cycles (1 cycle is 21 days) ]
    To determine the safety of tazemetostat in patients treated with 8 cycles of R-CHOP 21

  • Phase II : Complete Response Rate [ Time Frame: 8 cycles (1 cycle is 21 days) ]
    Complete response rate as determined by Cheson IWG 2014: Lugano Classification (Deauville scale 1-3)


Secondary Outcome Measures:
  • Phase I : Serum concentration of CHOP components in presence/absence of Tazemetostat [ Time Frame: Change between baseline - 1 month ]
  • Phase I : Serum concentration of Tazemetostat and its metabolite (EZH 6930) in presence of CHOP [ Time Frame: Change between baseline - 1 month ]
  • Phase II : Overall response rate (ORR) [ Time Frame: 52 and 104 weeks and 2 years ]
  • Phase II : progression free survival (PFS) [ Time Frame: 52 and 104 weeks and 2 years ]
  • Phase II : serum concentration of R-CHOP components in the presence/absence of tazemetostat [ Time Frame: Change between baseline - 1 month ]
  • Phase II : serum concentration of tazemetostat and its metabolite (EZH-6930) in the presence of R-CHOP [ Time Frame: Change between baseline - 1 month ]

Estimated Enrollment: 133
Actual Study Start Date: October 2016
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epi-RCHOP

RCHOP + 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):

    8 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
Drug: Tazemetostat
Tablets 200 mg, to be administrated per os
Other Name: EPZ-6438
Drug: Rituximab
375 mg/m²/dose, D1
Other Name: Mabthera
Drug: Cyclophosphamide
750 mg/m²/dose, D1
Drug: Vincristine
1.4 mg/m²/dose (max 2 mg), D1
Drug: Doxorubicin
50 mg/m²/dose, D1
Drug: Prednisolone
40 mg/m2 in the morning D1 to D5

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 115 patients will be recruited and treated with tazemetostat at the MTD and RCHOP. Patients will receive 8 cycles of RCHOP every 21 days and tazemetostat at the MTD every day, starting on day 2 of cyle 1.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a untreated DLBCL de novo or transformed from indolent lymphoma (CD 20 positive) with Age-adjusted International Prognostic Index (aaIPI) ≥ 2
  • Age between 60 and 80 years included
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (0 or 1 only for phase Ib)
  • Sied informed consent
  • Life expectancy of ≥ 90 days (3 months) before starting tazemetostat
  • Adequate renal function as calculated by a creatinine clearance > 40 mL/min by local institutional formula
  • Adequate bone marrow function as defined as:

absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 X 10 G/L) Platelets ≥ 75,000/mm3 (≥ 75 X 10 G/L) without platelet transfusion dependency during the last 7 days Hemoglobin ≥ 9 g/dL (may receive transfusion)

  • 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 (≤ 5 X ULN if there is lymphoma involvement of the liver)
    • Patients with prior Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are eligible if for Hepatitis B detection, surface antigen is negative and/or HBV DNA is undetectable, and if for Hepatitis C detection, HCV RNA is undetectable.
  • Left ventricular ejection fraction (LVEF) > 50% of echocardiography or multiple gated acquisition (MUGA) scan
  • Adequate tissue for central retrospective testing of EZH2 mutation status and cell of origin (15 slides of tumor biopsy must be available at screening)
  • Males with partners of childbearing potential must agree to use reliable forms of contraception

Exclusion Criteria:

  • Symptomatic central nervous system or meningeal involvement
  • Contraindication to any drug contained in the chemotherapy regimen
  • Prior treatment with tazemetostat or other inhibitor of EZH2
  • 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 taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's wort) or known substrates of CYP2C9
  • Patients unwilling to exclude Seville oranges, grapefruit juice and or grapefruit from diet
  • Major surgery within 4 weeks before first dose of study drug (minor procedures such as transcutaneous biopsy, central line placement are permitted within 2 weeks of enrollment)
  • Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition that would harm ability to take tazemetostat
  • 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
  • Prolonged Fridericia's Corrected QT Interval (QTcF) >480 msec
  • Active uncontrolled infection requiring systemic therapy
  • Congenital immunodeficiency or known HIV (human immunodeficiency virus infection)
  • Any other major illness that in the investigator's judgement, will substantially increase the risk associated with the patient's participation in the study
  • Patients who have undergone a solid organ transplant
  • Previous treatment for B cell lymphoma, except low dose radiotherapy for follicular lymphoma and glucocorticoids (no more than 14 days before inclusion, 1 mg/kg/day maximum dose)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02889523


Contacts
Contact: Alexia Schwartzmann alexia.schwartzmann@lysarc.org

Locations
France
CHRU Lille - Hôpital Claude Huriez Recruiting
Lille Cedex, France, 59037
Contact: Franck MORSCHHAUSER, Pr         
Principal Investigator: Franck MORSCHHAUSER, Pr         
CHU de Nantes - Hôtel Dieu Recruiting
Nantes, France, 44093
Contact: Steven LE GOUILL, Pr         
Principal Investigator: Steven LE GOUILL, Pr         
CHU Lyon Sud Recruiting
Pierre-Bénite Cedex, France, 69495
Contact: Gilles SALLES, Pr         
Principal Investigator: Gilles SALLES, Pr         
Centre Henri Becquerel Recruiting
Rouen, France, 76000
Contact: Hervé TILLY, Pr         
Principal Investigator: Hervé TILLY, Pr         
Institut Gustave Roussy Recruiting
Villejuif, France, 94085
Contact: Vincent RIBRAG, Pr         
Principal Investigator: Vincent RIBRAG, Pr         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Epizyme, Inc.
Investigators
Principal Investigator: Vincent Ribrag, MD Institut Gustave Roussy Cancer Campus Grand Paris
Principal Investigator: Clémentine Sarkozy, MD Centre Hospitalier Lyon Sud
  More Information

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT02889523     History of Changes
Other Study ID Numbers: Epi-RCHOP
First Submitted: July 11, 2016
First Posted: September 5, 2016
Last Update Posted: July 12, 2017
Last Verified: July 2017

Keywords provided by The Lymphoma Academic Research Organisation:
Front line therapy
Age-adjusted International Prognostic Index (aa-IPI) >1
60 to 80 years

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Vincristine
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents