A Phase II Study of Epigenetic Priming Using Azacitidine Followed by Rituximab-GDP Immunochemotherapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- azacitidine plus R-GDP
- Conditions
- Diffuse Large B Cell Lymphoma
- Sponsor
- Seoul National University Hospital
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Objective response rate
- Last Updated
- 7 years ago
Overview
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.
Detailed Description
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). This study is designed with the expectation of correction of aberrant hypermethylation of tumor suppressor genes by preceding use of low dose azacitidine thereby re-sensitizing chemosensitivity of tumor cells. Patients who were treated with from 1 to 4 lines of prior therapies for relapsed/refractory DLBCL wee eligible. Planned initial doses of the current regimen are as follows; 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 cisplatin 70 mg/m2 I.V. D8 Patients will be treated every 21 days as one cycle, and up to 6 cycles of treatment will be conducted. Especially, first 3\~6 patients will be regarded as 'lead-in safety cohort' and their safety will be reviewed by an independent data and safety monitoring board (DSMB). 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.
Investigators
Sung-Soo Yoon
Professor
Seoul National University Hospital
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
- •in cases of patients who are positive for hepatitis C antibody, patients will be allowed if they satisfy all other inclusion criteria and without evidence of liver cirrhosis (irrespective of HCV RNA titer)
- •patients who were diagnosed HCV less than 6 months before screening period will be excluded unless they have negative result for HCV RNA
Arms & Interventions
Treatment arm
This study is sing-arm study. Therefore, all enrolled patients will be treated with azacitidine plus R-GDP regimen
Intervention: azacitidine plus R-GDP
Outcomes
Primary Outcomes
Objective response rate
Time Frame: up to 3 years
according to Lugano response criteria for non-Hodgkin lymphoma
Secondary Outcomes
- Safety (adverse events and severe adverse events)(up to 3 years)
- Progression-free survival(up to 3 years)
- Overall survival(up to 3 years)
- Complete response rate(up to 3 years)