Azacitidine and Rituximab-GDP Immunochemotherapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT03719989 | Unknown Phase 2 DMC

• 1 other identifier: EPIC
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial aims at evaluating the efficacy and safety of azacitidine followed by rituximab-GDP immunochemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients who were treated with from 1 to 4 lines of prior therapies for relapsed/refractory DLBCL wee eligible. azacitidine will be treated one week prior to conventional rituximab-gemcitabine, dexamethasone, cisplatin (R-GDP) immunochemotherapy. Patients will be treated every 21 days as one cycle, and up to 6 cycles. The primary endpoint of this study is objective response rate according to the Lugano response criteria for non-Hodgkin lymphoma, and secondary endpoints are safety, complete response, progression-free survival, and overall survival.

Conditions

Diffuse Large B Cell Lymphoma; Relapsed Non Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  according to Lugano response criteria for non-Hodgkin lymphoma

  up to 3 years

Secondary Outcomes (4)

• Safety (adverse events and severe adverse events)

  up to 3 years

• Complete response rate

  up to 3 years

• Progression-free survival

  up to 3 years

• Overall survival

  up to 3 years

Study Arms (1)

Treatment arm

EXPERIMENTAL

This study is sing-arm study. Therefore, all enrolled patients will be treated with azacitidine plus R-GDP regimen

Drug: azacitidine plus R-GDP

Interventions

azacitidine plus R-GDP DRUG

azacitidine S.C 25 mg/m2 D1,2,3,4,5 rituximab I.V. 375 mg/m2 D8 gemcitabine I.V. 1,000 mg/m2, D8,15 dexamethasone I.V. or P.O. 40 mg D8,9,10,11 every 21 days, up to 6 cycles

Also known as: N/E

Treatment arm

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age from 19 to 75 years
• diagnosed as diffuse large B-cell lymphoma according to the World Health Organization 2016 criteria
• with any measurable lesion by radiologic studies (direct measurement is allowed in cases of (sub)cutaneous lesions)
• patients who were initially treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or other rituximab-containing immunochemotherapy and relapsed or refractory to prior treatment
• previously treated with from1 to 4 lines of therapy
• autologous stem cell transplant (ASCT) will be counted as 1 line of therapy
• in cases of previously treated with ASCT, patients 1) who elapsed at 60 days and 2) who have lower risk of severe bone marrow suppression and infectious complication, judged by physician
• ASCT ineligible or no further plan of ASCT due to previous transplantation
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0\~2
• Hb ≥ 8.0 g/dL, absolute neutrophil count (ANC) ≥ 1,000/mm3, Platelet ≥ 100,000/mm3 prior to enrollment
• correction of Hb by transfusion will be allowed
• in cases of bone marrow involvement, patients will be included if they have ANC ≥ 500/mm3, Platelet ≥ 50,000/mm3 and no significant infection risk or transfusion dependency
• Glomerular Filtration Rate \> 60 mL/min calculated according to Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) equation, and total bilirubin \< 2.5 mg/dL, aspartate amino-transferase (AST) and alanine amino- transferase (ALT) \< x3 upper limit of normal (ULN)
• In cases of hepatic involvement of DLBCL, AST or ALT \< x5 ULN will be allowed
• In cases of Gilbert syndrome, Direct bilirubin \< 2.5 ULN will be allowed

You may not qualify if:

• primary or secondary central nervous system DLBCL
• patients with or strongly suggestive of lymphomatous involvement on eye, epidural area, kidney/adrenal gland, breast, testes, or uterus
• intravascular DLBCL
• DLBCL transformed from low grade lymphoma
• high grade B-cell lymphomas other than DLBCL: primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma not otherwise specified (NOS), high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 6 (BCL6) rearrangements, B-cell lymphoma, unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma
• human immunodeficiency virus (HIV) associated DLBCL
• patients with liver cirrhosis of Child-Pugh Classification B or higher, or active hepatitis B (HBV) or hepatitis C (HCV) infection
• in cases of patients who are positive for HBsAg or HBcAb immunoglobulin G (IgG) but no evidence of active infection, patients who are negative for HBV DNA will be allowed only with adequate anti-viral prophylaxis
• patients who were diagnosed HCV less than 6 months before screening period will be excluded unless they have negative result for HCV RNA
• patients with active infection treated with anti-microbial agents
• patients who were diagnosed malignancy other than lymphoma, either actively treated or have been received chemotherapy or radiation therapy less than 3 years from the time of enrollment
• Major surgery within 21 days (open laparotomy for diagnostic biopsy will be exempted)
• patients who underwent hypersensitivity, severe allergic reaction or anaphylaxis to rituximab or other chimeric/humanized antibodies
• patients who underwent hypersensitivity, severe allergic reaction or anaphylaxis gemcitabine, azacitidine, or cisplatin
• severe congestive heart failure, unstable heart or pulmonary diseases

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Related Publications (1)

• Kim DH, Kong JH, Hong J, Byun JM, Shin DY, Koh Y, Kim I, Park J, Do YR, Kim JA, Kim WS, Shin HJ, Yoon SS. Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study. Ther Adv Hematol. 2025 Jul 11;16:20406207251349361. doi: 10.1177/20406207251349361. eCollection 2025.

  PMID: 40656663 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Junshik Hong, MD

CONTACT

82-2-2072-3383; alertjun@hanmail.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 25, 2018
• Study Start: December 1, 2018
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2023
• Last Updated: October 25, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)