Relapsed or refractory diffuse large B cell lymphoma (DLBCL).
Conditions
Sponsors
National and Kapodostrian University of Athens
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed and dated written informed consent prior to performing any study-specific procedures. - Adult patients, age range 18-65 years old, eligible for transplantation. Patients > 65 and = 70 years old with ECOG =2 and absence of comorbidities will be included in the study upon investigator’s judgment. - Histologically confirmed diagnosis of relapsed or refractory CD20 positive DLBCL. Diagnosis should be confirmed by immunophenotyping by staining paraffin embedded tissue sections with the following panel of markers: BCL2, CD5, CD10, CD3, CD4, CD8, BCL6, IRF4/MUM-1, Ki67, p53, ALK, HLA class I and HLA-DR. - First relapse after CR or less than PR after first line treatment. - Previous treatment with chemotherapy regimen containing anthracyclines with rituximab for at least 3 cycles. - ECOG Performance Status 0-2. - Life expectancy of more than 3 months. - Adequate bone marrow, liver and renal function: * Hemoglobin = 9.0 g/dL. * Absolute neutrophil count (ANC) = 1500/µl. * Platelet count = 100000/µl. * Total bilirubin = 1.5 X ULN. * AST and ALT = 2.5 x ULN. * Alkaline phosphatase = 1.5 x ULN. * Serum creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Burkitt, mantle-cell and T cell Lymphoma. - CD20 negative DLBCL. - Central nervous system and/or bone marrow involvement. - Prior transplantation. - No prior treatment with anthracycline-containing regimen. - Treatment with rituximab or treatment with rituximab for less than 3 cycles. - Other past or current malignancy with the exception of cured (minimum 2 years prior entry) basal cell carcinoma of the skin, or in situ carcinoma of the cervix or the breast. - History of significant cerebrovascular disease or event with significant symptoms or sequelae. - Any major organ dysfunction. - History of HIV infection. - Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). - Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. - Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the patient will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the patient can be included. - Positive serology for hepatitis C (HC) defined by positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result. - Previous treatment or known or suspected hypersensitivity to ofatumumab. - Known or suspected hypersensitivity to any of the components of the ESHAP regimen. - Treatment with any investigational drug substance or experimental therapy within 4 weeks prior to the 1st treatment cycle, or current participation in any other interventional clinical trial. - Known or suspected inability to comply with study protocol. - Lactating women, women with a positive pregnancy test at screening or women (of childbearing potential) as well as men with female partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as abstinence, oral hormonal birth control, hormonal birth control injections, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is sole partner for that patient. The double barrier method can be used in regions where considered acceptable and adequate (condom or occlusive cap plus spermicidal agent).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of the ofatumumab-ESHAP regimen in terms of overall response rate (ORR).;Secondary Objective: 1. To evaluate secondary efficacy parameters of the ofatumumab-ESHAP regimen [complete response (CR), overall survival (OS) and progression-free survival (PFS)]. 2. To evaluate the safety of the ofatumumab-ESHAP regimen. 3. To evaluate parameters related to the autologous stem cell transplantation [transplantation-related mortality (TRM), OS, PFS]. ;Primary end point(s): Overall response rate (ORR): Percentage of patients with at least partial remission, according to the IWG response criteria.;Timepoint(s) of evaluation of this end point: At the end of the clinical trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Complete remission rate (CR): Percentage of patients with complete remission, according to the IWG response criteria. - Median Overall Survival (OS): Median time to death from any cause. - Median progression free survival (PFS): Median time to disease progression or death from DLBCL. - Rate of occurrence of AEs/SAEs/ADRs/SADRs: Percentage of patients who received at least one dose of treatment and experienced a given AE/SAE/ADR/SADR. - Stem-cell mobilization capacity: Percentage of patients with at least 2x106 collected CD34+ cells/kg. - Transplantation-related mortality (TRM) rate: Percentage of the patients who underwent ASCT who died of causes related to the transplantation.;Timepoint(s) of evaluation of this end point: At the end of the clinical trial. | — |
Countries
Greece
Contacts
Public ContactPrincipal Investigator
National and Kapodostrian University of Athens
Outcome results
None listed