Clinical Trials /

Phase III Study of Tucidinostat in Combination With R-CHOP in Patients With Newly Diagnosed Double-Expressor DLBCL

NCT04231448

Description:

Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase inhibitor. This Randomized, Double-blind, Placebo-controlled Phase 3 trail is studying the efficacy and safety of Tucidinostat, in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed MYC/BCL2 Double-Expressor Diffuse Large B-cell Lymphoma.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Study of Tucidinostat in Combination With R-CHOP in Patients With Newly Diagnosed Double-Expressor DLBCL
  • Official Title: Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Tucidinostat in Combination With R-CHOP in Patients With Newly Diagnosed MYC/BCL2 Double-Expressor DLBCL

Clinical Trial IDs

  • ORG STUDY ID: CDM302
  • NCT ID: NCT04231448

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone)CR-CHOP
TucidinostatCR-CHOP
PlaceboR-CHOP

Purpose

Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase inhibitor. This Randomized, Double-blind, Placebo-controlled Phase 3 trail is studying the efficacy and safety of Tucidinostat, in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed MYC/BCL2 Double-Expressor Diffuse Large B-cell Lymphoma.

Detailed Description

      The primary objective is to evaluate if the addition of Tucidinostat to rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) prolongs event-free
      survival (EFS) compared with R-CHOP alone in subjects with newly diagnosed MYC/BCL2
      Double-Expressor subtype of DLBCL selected by IHC and FISH.
    

Trial Arms

NameTypeDescriptionInterventions
CR-CHOPExperimental
  • R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone)
  • Tucidinostat
R-CHOPPlacebo Comparator
  • R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone)
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Each potential subject must satisfy all of the following criteria to be enrolled in
             the study.

               1. Male or female, age ≥ 18 years and ≤80 years.

               2. No prior treatment for diffuse large B cell lymphoma(DLBCL), including
                  hemotherapy, immunotherapy; radiotherapy (excluding local radiotherapy);
                  monoclonal antibody therapy; surgical treatment (excluding biopsy)

               3. Histological or cytological confirmation of DLBCL

               1. CD20-positive DLBCL;

               2. Myc≥40% as well as Bcl-2≥50% through immunohistochemistry;

               3. Not with double (BCL-2 and c-MYC gene rearrangement) or triple (BCL-2, BCL-6, and
                  c-MYC gene rearrangement) hit by FISH.

        The verification of DLBCL will be based on local pathology report.15-20 unstained slides
        must be sent to the central laboratory for retrospective confirmation.

        4.At least one positive lesion according to the Lugano Classification by fluorodeoxyglucose
        (FDG) positron emission tomography (PET)-computed tomography(CT).

        5.Lymphoma International PrognosisIndex (IPI) score of 2,3,4. 6.Eastern Cooperative
        Oncology Group performance status grade of 0, 1, or 2. 7.Laboratory criteria are as follows
        except that caused by lymphoma assessed by the investigator (without receiving any
        supportive treatment for the following parameters within 2 weeks from the last dose prior
        to study entry):

        (1)Hematology values:Hemoglobin (Hb)≥90g/L ; Absolute neutrophil count (ANC) ≥1.5×109/L ;
        platelets ≥90×109/L (2)Biochemical values: Serum creatinine ≤1.5×upper limit of
        normal(ULN); Total bilirubin ≤1.5 × ULN; Alanine aminotransferase (ALT), Aspartate
        aminotransferase (AST) ≤2.5×ULN(ALT,AST≦5×ULN if liver involved).

        8.Expected survival≥6 months. 9.All patients must have signed an informed consent document.

        Exclusion Criteria:

          -  Any potential subject who meets any of the following criteria will be excluded from
             participating in the study.

               1. Presence of CNS involvement.

               2. Patients with primary DLBCL of the central nervous system (CNS),or secondary
                  lymphoma of the central nervous system, or Primary mediastinal (thymic) large
                  B-cell lymphoma, or Primary effusion lymphoma, or B-cell lymphoma,
                  unclassifiable, with features intermediate between DLBCL and classical Hodgkin
                  lymphoma, or Primary cutaneous DLBCL, leg type, or indolent lymphoma, or Burkitt
                  lymphoma, or EBV-positive mucocutaneous ulcer, or DLBCL associated with chronic
                  inflammation, or Lymphomatoid granulomatosis, or Intravascular large B-cell
                  lymphoma, or ALK-positive large B-cell lymphoma, or Plasmablastic lymphoma, or
                  HHV8-positive DLBCL, NOS, or primary testicular DLBCL.

               3. Patients with transformed lymphoma.

               4. History of organ transplantation or hematopoietic stem cell transplantation.

               5. Patients planned for autologous or allogeneic transplant as consolidation in
                  first line.

               6. Patients with any other malignancy, except patients with a history of curatively
                  treated basal or squamous cell carcinoma or in situ carcinoma of the cervix at
                  any time prior to the study are eligible.

               7. Prior treatment with cytotoxic drugs for another condition (e.g., rheumatoid
                  arthritis) or prior use of an anti-CD20 antibody within 5 years of the start of
                  Cycle 1.

               8. Prior use of any monoclonal antibody within 3 months of the start of Cycle 1.

               9. Any investigational therapy within 3 months prior to the start of Cycle 1.

              10. History of severe allergic or anaphylactic reactions to humanized or murine
                  monoclonal antibodies or known sensitivity or allergy to murine products.

              11. Contraindication to any of the individual components of CHOP.

              12. Corticosteroid use > 30 mg/day of prednisone or equivalent, for purposes other
                  than lymphoma symptom control:

               1. Patients receiving corticosteroid treatment with ≤ 30 mg/day of prednisone or
                  equivalent must be documented to be on a stable dose of at least 4 weeks'
                  duration prior to randomization (Cycle 1, Day 1).

               2. If glucocorticoid treatment is urgently required for lymphoma symptom control
                  prior to the start of study treatment, prednisone 100 mg or equivalent could be
                  given for a maximum of 5 days, but all tumor assessments must be completed prior
                  to start of glucocorticoid treatment.

             13.Ongoing serious central nervous system disease or peripheral neuropathy, such as
             progressive multifocal leukoencephalopathy.

             14.Have uncontrolled or significant cardiovascular disease, including:

               1. Grade II or higher Congestive heart failure, unstable angina pectoris, myocardial
                  infarction (New York Heart Association Functional Classification ) within 6
                  months prior to study entry; or arrhythmia requiring treatment, or Left
                  Ventricular Ejection Fraction (LVEF) < 50% during screening stage.

               2. Primary cardiomyopathy (dilated cardiomyopathy, hypertrophic cardiomyocyte,
                  arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy,
                  et,al).

               3. History of significant QT interval prolongation, or Corrected QT Interval
                  QTc≥450ms(male), QTc≥470ms(female)at screening.

               4. Symptomatic coronary heart disease requiring treatment.

               5. Any other cardiovascular disease which is inappropriate for the study according
                  to investigators' judgment.

             15.History of interstitial lung disease(ILD), or with ongoing signs and symptoms by CT
             or MRI at the time of screening.

             16.Patients with factors that could affect oral medication (such as dysphagia, chronic
             diarrhea, intestinal obstruction etc), or undergone gastrectomy.

             17.History of deep vein thrombosis or pulmonary embolism. 18.History of active
             bleeding within 2 months prior to the start of Cycle 1;or patients receiving
             anticoagulation therapy; or patients with evidence of bleeding potential according to
             investigators' judgment ( esophageal varices, active ulcer, or fecal occult blood test
             positive etc. ). Patients with bleeding led by lymphoma according to investigators'
             judgment are eligible.

        19.6 weeks or less from the last major surgery that involved crucial organs, or with any
        other factors impede postoperative recovery according to investigators' judgment.

        20.Known active infection, or active and uncontrolled hepatitis B infection(HBV), hepatitis
        C Virus(HCV), human immunodeficiency virus (HIV)/AIDS (Acquired Immune Deficiency
        Syndrome), or any other serious infection. (active infection defined as any major episode
        of infection requiring systemic treatment; Patients with occult or prior HBV may be
        included if HBV DNA is undetectable.) 21.Any mental or cognitive disorder, that would
        impair the ability to understand the informed consent document, or limit compliance with
        study requirements/ treatment.

        22.Drug or alcohol abuse. 23.Women of childbearing potential and men who are sexually
        active not willing to practice a highly effective method of birth control during and after
        the study consistent with local regulations regarding the use of birth control methods for
        subjects participating in clinical trials.These restrictions apply for 12 months after the
        last dose of rituximab or 12 weeks after the last dose of study drug, whichever is later.
        Pregnancy or lactation.

        24.Any other condition which is inappropriate for the study according to investigators'
        judgment.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event Free Survival (EFS)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the duration from the date of randomization to the date of disease progression, relapse from CR , initiation of subsequent systemic antilymphoma therapy for residual disease, or death, whichever occurs first.

Secondary Outcome Measures

Measure:Complete Response Rate(CRR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Defined as the proportion of subjects with measurable disease who achieve CR.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined as the duration from the date of randomization to the date of progression, relapse from CR, or death, whichever occurred first.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:defined as the duration from the date of randomization to the date of the participant's death
Measure:Disease-Free Survival (DFS)
Time Frame:Up to approximately 5 years
Safety Issue:
Description:Defined for patients achieving CR as the period from the date of the initial CR until the date of relapse or death from any cause.
Measure:Safety of Tucidinostat when combined with R-CHOP
Time Frame:Up to approximately 5 years
Safety Issue:
Description:All adverse events occurring during or after the first treatment will be summarized by treatment arm and NCI CTCAE grade.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Chipscreen Biosciences, Ltd.

Last Updated

January 14, 2020