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

NCT04231448 | Completed Phase 3 DMC

• 1 other identifier: CDM302
• Study Type: interventional
• Target: 423
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS)

  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.

  Up to approximately 5 years

Secondary Outcomes (5)

• Complete Response Rate(CRR)

  Up to approximately 3 years

• Progression-Free Survival (PFS)

  Up to approximately 5 years

• Overall Survival (OS)

  Up to approximately 5 years

• Disease-Free Survival (DFS)

  Up to approximately 5 years

• Safety of Tucidinostat when combined with R-CHOP

  Up to approximately 5 years

Study Arms (2)

CR-CHOP

EXPERIMENTAL

Drug: R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone); Drug: Tucidinostat

R-CHOP

PLACEBO COMPARATOR

Drug: R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone); Drug: Placebo

Interventions

R-CHOP(Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) DRUG

R-CHOP : rituximab 375 mg/m2 IV, cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 IV \[maximum total 2 mg\], and prednisone \[or equivalent\] 100 mg orally as the background therapy for 6 cycles (21 days/cycle).

CR-CHOP; R-CHOP

Tucidinostat DRUG

Tucidinostat ：30 mg was given orally after breakfast on day 1, day 4, day 8, day 11 in a 21-day cycle，for 6 cycles. After cycle 6 patients who are evaluated as complete response will receive 24 weeks additional administrations of Tucidinostat on day 1, day 4, day 8, day 11 in a 21-day cycle.

CR-CHOP

Placebo DRUG

Placebo：30 mg was given orally after breakfast on day 1, day 4, day 8, day 11 in a 21-day cycle，for 6 cycles. After cycle 6 patients who are evaluated as complete response will receive 24 weeks additional administrations of placebo on day 1, day 4, day 8, day 11 in a 21-day cycle.

R-CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each potential subject must satisfy all of the following criteria to be enrolled in the study.
• Male or female, age ≥ 18 years and ≤80 years.
• No prior treatment for diffuse large B cell lymphoma(DLBCL), including hemotherapy, immunotherapy; radiotherapy (excluding local radiotherapy); monoclonal antibody therapy; surgical treatment (excluding biopsy)
• Histological or cytological confirmation of DLBCL
• <!-- -->
• CD20-positive DLBCL;
• Myc≥40% as well as Bcl-2≥50% through immunohistochemistry;
• 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.
• At least one positive lesion according to the Lugano Classification by fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography(CT).
• 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).
• Expected survival≥6 months. 9.All patients must have signed an informed consent document.

You may not qualify if:

• Any potential subject who meets any of the following criteria will be excluded from participating in the study.
• Presence of CNS involvement.
• 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.
• Patients with transformed lymphoma.
• History of organ transplantation or hematopoietic stem cell transplantation.
• Patients planned for autologous or allogeneic transplant as consolidation in first line.
• 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.
• 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.
• Prior use of any monoclonal antibody within 3 months of the start of Cycle 1.
• Any investigational therapy within 3 months prior to the start of Cycle 1.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.
• Contraindication to any of the individual components of CHOP.
• Corticosteroid use \> 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control:
• <!-- -->
• 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).

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (2)

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Location

Shanghai JiaoTong University School of Medicine，Ruijin Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Weili Zhao, Professor

  Shanghai JiaoTong University School of Medicine，Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Jun Zhu, Professor

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: May 21, 2020
• Primary Completion: January 10, 2023
• Study Completion: June 29, 2025
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)