Inclusion Criteria:

          1. Histologically proven CD20+ aggressive non-Hodgkin lymphoma (diffuse large B-cell
             lymphoma (DLBCL), de novo or transformed DLBCL from previously untreated low grade
             non-Hodgkin lymphoma or grade 3b follicular lymphoma) as per the World Health
             Organization (WHO) 2016 criteria

          2. Relapsed or refractory disease, defined as follows:

               1. Patients eligible for ASCT who failed to achieve a Complete Response (CR) after
                  at least one salvage therapy (eg, Rituximab-Etoposide- Methylprednisolone -
                  Cytarabine - Cisplatin (R-ESHAP) or Rituximab- Dexamethasone- High-dose
                  Cytarabine - Cisplatin (R-DHAP), patients who were previously refractory to
                  Rituximab-Ifosfamide-Cytarabine-Etoposide (R-ICE) (stable disease or progressive
                  disease) are not eligible to the study)

               2. Or patients in first relapse after Autologous Stem Cell Transplant (ASCT)

               3. 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 > or =18 years

          4. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2

          5. Subjects must have evaluable disease based on positron emission tomography (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

        Exclusion Criteria:

          1. Any other histological type of lymphoma (Burkitt lymphoma, mantle-cell lymphoma…)

          2. Any history of previously treated indolent non-Hodgkin lymphoma

          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:

               1. Absolute neutrophil count (ANC) < 1.0 G/L

               2. Platelet count < 100 G/L

               3. Creatinine clearance < 40 mL/min for patients < 70 y, or creatinine clearance <
                  60 mL/min for patients > or = 70 y, by Modification of Diet in Renal Disease
                  (MDRD) method.

               4. Total bilirubin level > 1,5 x Upper Limit of Normal (ULN)

               5. Serum ASpartate Transaminase (AST) or ALanine Transaminase (ALT)> 2,5x ULN

          7. Known Human Immunodeficiency Virus (HIV) positive

          8. Active hepatitis C virus (HCV) (Positive HCV serology with positive Polymerase Chain
             Reaction (PCR) for HCV RNA)

          9. Active hepatitis B (HB) :

               1. HBsAg positive

               2. HBsAg negative, Ac anti-HBs positive and/or Ac anti-HB core (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 HB virus DNA is
                  negative)

         10. Cumulative dose of doxorubicine or equivalent > 450mg/m2

         11. Left ventricular ejection fraction (LVEF) < 50% measured by echocardiography or
             isotopic method

         12. Congestive heart failure (any stage from New York Heart Association (NYHA)
             classification)

         13. Uncontrolled arterial hypertension

         14. Severe rhythmic heart disease

         15. Uncontrolled ischemic heart disease, including patients with stable angina

         16. Significant valvular heart disease

         17. History of a myocardial infarction within 6 months prior to enrolment

         18. Pregnant or lactating females

         19. Prior history of malignancies with the exception of non-melanoma skin tumors (basal
             cell or squamous cell carcinoma) or in situ cervical carcinoma

         20. Any serious active disease or co-morbid medical condition according to the
             investigator's decision

         21. Adult person unable to provide informed consent because of intellectual impairment,
             any serious medical condition, laboratory abnormality or psychiatric illness

         22. Use of any standard or experimental anti-cancer drug therapy within 28 days before the
             first study drug administration

         23. Use of corticosteroids prior to baseline PET-CT

         24. Person deprived of his/her liberty by a judicial or administrative decision

         25. Person hospitalized without consent

         26. Adult person under legal protection