Patients with CD20-positive relapsed or refractory aggressive non-Hodgkin lymphoma MedDRA version: 20.0 Level: HLT Classification code 10029608 Term: Non-Hodgkin's lymphomas unspecified histology aggressive System Organ Class: 100000004851
Conditions
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 - Histologically proven CD20+ aggressive non-Hodgkin lymphoma (diffuse large B-cell lymphoma (DLBCL), de novo or transformed DLBCL from previously low grade non-Hodgkin lymphoma or grade 3b follicular lymphoma) note previously treated with more than 2 lines of cytotoxic agents before transformation, as per the WHO 2016 criteria agents 2 - Relapsed or refractory disease, defined as follows: a. Patients eligible for ASCT who failed to achieve a CR after at least one salvage therapy (eg, R-ICE, R-ESHAP, or R-DHAP), patients who were previously refractory to R-ICE (stable disease or progressive disease) are not eligible to the study). b. Or patients in first relapse after ASCT c. Or patients not eligible for ASCT who failed to achieve a CR after at least one prior treatment (and no more than 4 previous lines) or in relapse after at least one prior treatment (and no more than 4 previous lines). 3 - Age between 18 and 79 years included, at the time of informed consent signature 4 - Eastern Cooperative Oncology Group (ECOG) performance status under or equal to 2 5 - Subjects must have evaluable disease based on PET-CT scan 6 - Minimum life expectancy of 6 months 7 - Signed written informed consent 8 - Patient covered by any social security system 9 - Men must agree to use a barrier method of contraception during the treatment period and until 6 months after the last dose of chemotherapy 10 - Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of chemotherapy Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1 - Any other histological type of lymphoma (Burkitt lymphoma, mantle-cell lymphoma…) 2- Any history of indolent NHL previously treated by more than 2 lines of cytotoxic agents before transformation 3 - Symptomatic central nervous system or meningeal involvement by the lymphoma 4 - Contraindication to any drug contained in the Pixantrone with rituximab, ifosfamide and etoposide regimen 5 - Treatment with any investigational drug within 28 days before the first study drug administration 6 - Any of the following lab abnormalities unless related to the lymphoma or bone marrow infiltration: a. Absolute neutrophil count (ANC) 1,5xULN e. Serum AST/SGOT or ALT/SGPT > 2,5x ULN 7 - Known HIV positive 8 - Active hepatitis C (Positive HCV serology with positive PCR for HCV RNA) 9 - Active hepatitis B : a. HBsAg positive b. HBsAg negative, Ac anti-HBs positive and/or Ac anti-HBc positive (Patients who are seropositive due to a history of hepatitis B vaccine are eligible. Patients with Ac anti-HBs positive and/or Ac anti-HBc positive and no history of hepatitis B vaccine are eligible only if PCR for VHB DNA is negative) 10 - Cumulative dose of doxorubicine or equivalent > 450mg/m2 11 - Left ventricular ejection fraction (LVEF) < 45% measured by echocardiography or isotopic method 12 - Congestive heart failure NYHA stage III or IV 13 - History of a myocardial infarction within 6 months prior to enrolment 14 - Pregnant or lactating females 15 - Prior history of other malignancies with the exception of non-melanoma skin tumors (basal cell or squamous cell carcinoma) or in situ cervical carcinoma unless the patient has been free of the disease for = 3 years after curative treatment including surgical resection, chemotherapy or radiotherapy. 16 - Any serious active disease or co-morbid medical condition according to the investigator’s decision 17 - Adult person unabled to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness 18 - Use of any standard or experimental anti-cancer drug therapy within 28 days before the first study drug administration and any evolutive toxicity that could interfere with the assessment of the safety profile of the trial 19 - Use of corticosteroids prior to baseline PET-CT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the efficacy of Pixantrone with rituximab, ifosfamide and etoposide as measured by the overall metabolic response (OMR) rate after 2 cycles of treatment or at permanent treatment discontinuation, whichever occurs first.;Secondary Objective: - To assess the efficacy of Pixantrone with rituximab, ifosfamide and etoposideas measured by the response rates, PFS and OS - To assess the safety of pixantrone with rituximab, ifosfamide and etoposide - To assess the transformation rate from PMR into CMR at the end of treatment for patients in PMR after 2 cycles who have not received transplant - To assess the feasibility of performing an autologous stem cell transplantation afterPixantrone with rituximab, ifosfamide and etoposide in patients who intend to undergo ASCT - To assess the success of stem cell collection after treatment;Primary end point(s): The primary efficacy endpoint is the assessment of the Overall Metabolic Response (OMR) rate by local investigator based on PET-CT scan according to Lugano classification (Cheson B. et al, JCO 2014) ;Timepoint(s) of evaluation of this end point: After 2 cycles or at permanent treatment discontinuation, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Complete Metabolic Response (CMR) rate according to the local investigator - OMR and CMR rate according to the central review - OMR and CMR rate according to the local investigator - PET results according to local investigator and central review - Transformation rate from PMR into CMR - Progression-free survival (PFS) - Overall survival (OS) - Rate of ASCT - Rate of successful stem cell collection - Adverse Events (AEs) and Serious Adverse Events (SAEs);Timepoint(s) of evaluation of this end point: CMR rate : - local investigator = after 2 cycles or at permanent treatment discontinuation (PTD) + timepoint of interest*/ EOT - central review = after 2 cycles or PTD OMR rate : - central review = after 2 cycles or PTD - local investigator = PTD or timepoint of interest*/EOT PET results : after 2 cycles and EOT Transformation rate from PMR into CMR : EOT for patients not eligible for ASCT PFS, OS, Rate of ASCT, Rate of successful stem cell collection, AEs and SAEs: end of study * Timepoint of interest : - after 2 cycles for patients in CMR or PMR after 2 cycles eligible for ASCT - after 6 cycles for patients in CMR or PMR after 2 cycles not eligible for ASCT - after 2 cycles for patients who did not respond after 2 cycles | — |
Countries
Belgium, France
Contacts
Public ContactClinical Project Manager L. MELGAR
LYSARC
Outcome results
None listed