Phase 1/2 Study of the Combination of Pixantrone, Etoposide, Bendamustine and, in CD20 Positive Tumors, Rituximab in Patients With Relapsed Aggressive Non-Hodgkin Lymphomas of B- or T-cell Phenotype - the P[R]EBEN Study

Phase 1/2 Study of the Combination of Pixantrone, Etoposide, Bendamustine and, in CD20 Positive Tumors, Rituximab in Patients With Relapsed Aggressive Non-Hodgkin Lymphomas of B- or T-cell Phenotype - the P[R]EBEN Study

This is a phase 1/2 open label study to assess the safety and efficacy of pixantrone in combination with bendamustine, etoposide and , for CD20 positive B-cell lymphomas, rituximab (P[R]EBEN), in patients with relapsed aNHL of B- or T-cell phenotype.

This is a phase 1/2 open label study to assess the safety and efficacy of pixantrone in combination with bendamustine, etoposide and , for CD20 positive B-cell lymphomas, rituximab (P[R]EBEN), in patients with relapsed aNHL of B- or T-cell phenotype.

Inclusion Criteria:

• Patients with a histologically confirmed relapse of an aggressive lymphoma of T- or B-cell phenotype (including follicular lymphoma grade 3b). For excluded histological entities see 'Exclusion criteria'

• Phase 1 + Phase 2 'fit' patients:

  • Age 18-70 years at the time of inclusion
  • ECOG PS 0-1 at protocol entry
  • Deemed 'fit' by the treating physician

• Phase 2 'frail' patients:

  • Age 71-85 years at the time of inclusion and/or
  • ECOG PS 2-3 at protocol entry and/or
  • Deemed 'frail' by the treating physician

• At least six months response duration since last given course of treatment

• Estimated life expectancy of 3 months or longer

• Measurable disease

• Hemoglobin ≥ 8 g/dL (≥5 mmol/l)

• Platelets ≥ 100 x 109/L; ≥ 75 x 109/L permitted if bone marrow involvement

• Absolute neutrophil count ≥ 1.5 x 109/L; ≥ 1.0 x 109/L permitted if documented bone marrow involvement

• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); patients with proven Gilbert's syndrome (≤ 5 x ULN) may be enrolled.

• Serum glutamic-oxaloacetic transaminase (AST) and/or serum glutamic-pyruvic transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if elevation is due to hepatic involvement by lymphoma

• Serum creatinine ≤ 2 x ULNb

• Women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 12 months after the last administration of study drugs

• Male patients must use contraception for the duration of the study and 6 months after the last administration of study drugs if his partner is of childbearing potential

• Written informed consent

Exclusion Criteria:

• Patients with primary refractory disease (e.g. progressing under platinum-containing or similar salvage therapy) defined as < 6 months response duration from last given course of treatment.

• High-dose therapy with autologous stem cell rescue within the last 6 months prior to study entry.

• Following T-cell lymphoma entities:

  • T-cell lymphoblastic lymphoma
  • Hepatosplenic T-cell lymphoma
  • Extranodal NK/T, nasal type
  • Subcutaneous panniculitis-like
  • Primary cutaneous T-cell lymphoma
  • Primary leukemic T-cell lymphoma

• Following B-cell lymphoma entities:

  • Transformed indolent B-cell lymphomas
  • Post-transplant B-cell lymphoproliferative disease
  • HIV-associated B-cell lymphoma

• Concurrent severe and/or uncontrolled medical disease which is not lymphoma-related

• Left ventricular ejection fraction (LVEF) < 45%

• Suspected or documented central nervous system involvement by NHL

• Patients known to be antigen positive for HIV and/or hepatitis B and/or hepatitis C

• Patients with active, uncontrolled infections

• Vaccination with live, attenuated vaccines within 4 weeks of inclusion

• Pregnant and/or breastfeeding women

• History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma

• Known hypersensitivity to one or more of the study drugs

• Unwillingness or inability to comply with the protocol