Relapse of aggressive non-Hodgkin lymphoma of B and T-cell phenotype MedDRA version: 18.1 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 18.1 Level: HLGT Classification code 10025321 Term: Lymphomas non-Hodgkin's T-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Department of Hematology, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
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 performance score (PS) 0-1 at protocol entry (for ECOG definition see appendix A) - 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 (for ECOG definition see appendix A) and/or - Deemed ‘frail’ by the treating physician • Estimated life expectancy of 3 months or longer • Measurable disease • Hemoglobin = 8 g/dL (=5 mmol/l) (can be post transfusion) • 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 ULN • Written informed consent 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 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
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: o T-cell lymphoblastic lymphoma o Hepatosplenic T-cell lymphoma o Extranodal NK/T, nasal type o Subcutaneous panniculitis-like o Primary cutaneous T-cell lymphoma o Primary leukemic T-cell lymphoma • Following B-cell lymphoma entities: o Transformed indolent B-cell lymphomas o Post-transplant B-cell lymphoproliferative disease o 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 • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the MTD of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in ‘fit' patients with rel aNHL of B- or T-cell phenotype. Evaluate the ORR and PFS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine either at the identified MTD (P[R]EBEN-fit) in ‘fit’ patients or at the baseline dose level (P[R]EBEN-frail) in ‘frail’ patients with rel aNHL. Evaluate the CR, PR, duration of response, and OS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with B- or T-cell NHL. Evaluate the safety and tolerability of combination therapy with pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with aggressive B- or T-cell NHL. ;Secondary Objective: To perform molecular analyses at nucleic acid (DNA, RNA, microRNA) and protein level to see if specific molecular features can predict responder versus non-responder status. ;Primary end point(s): Phase 1 part of the trial: MTD of pixantrone, bendamustine and etoposide in ‘fit’ rel aNHL pts Phase 2 part of the trial: ORR in both ‘fit’ and ‘frail’ rel aNHL pts ;Timepoint(s) of evaluation of this end point: Phase 1 part of the trial: End of treatment cycle 2 of the last included patient Phase 2 part of the trial: End of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 part of the trial: • ORR • CRR • Duration of response (DOR) Phase 2 part of the trial: • Safety and tolerability of the P[R]EBEN combination regimen • CRR • DOR • PFS • OS • Successful bridging to allogeneic transplantation;Timepoint(s) of evaluation of this end point: End of treatment and after 5 years of follow-up | — |
Countries
Denmark, Finland, Korea, Republic of, Netherlands, Norway, Sweden
Contacts
Public ContactClinical Trial Office
Department of Hematology, Aarhus University Hospital
Outcome results
None listed