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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Malignant Lymphoma

Intervention / Treatment
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* Drug: PREBEN


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: PREBEN<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of pixantrone, bendamustine and etoposide in 'fit' relapsed aNHL pts (phase 1) |  | 1.5 yrs | 
| Objective ORR in both 'fit' and 'frail' relapsed aNHL pts (phase 2) |  | 4 yrs |