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