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

NCT ID: NCT02678299

Last Updated: 2022-08-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2025-12-31

Brief Summary

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

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.

Conditions

Malignant Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Group Type: EXPERIMENTAL

PREBEN

Intervention Type: DRUG

Interventions

PREBEN

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco d'Amore, MD DMSci

Role: PRINCIPAL_INVESTIGATOR

Dept. of Hematology, Aarhus University Hospital

Locations

Department of Hematology, Aarhus University Hospital

Aarhus, , Denmark

Department of Hematology, Copenhagen University Hospital

Copenhagen, , Denmark

Department of Hematology, Odense University Hospital

Odense, , Denmark

Helsinki University Hospital Comprehensive Cancer Center

Helsinki, , Finland

Jeroen Bosch Hospital

's-Hertogenbosch, , Netherlands

Meander Medical Center

Amersfoort, , Netherlands

Slingeland Hospital

Doetinchem, , Netherlands

Albert Schweitzer Hospital

Dordrecht, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Admiraal de Ruyter Hospital

Flushing, , Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Spaarne Ziekenhuis

Hoofddorp, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Haga Hospital, loc. Leyweg

The Hague, , Netherlands

Department of Oncology, Oslo University Hospital

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

Department of Oncology, St. Olavs Hospital

Trondheim, , Norway

Department of Oncology, Skåne University Hospital

Lund, , Sweden

Countries

Denmark; Finland; Netherlands; Norway; Sweden

Other Identifiers

2015-000758-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PREBEN

Identifier Type: -

Identifier Source: org_study_id