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

Malignant Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02678299
• Other study ID #: PREBEN
• Secondary ID: 2015-000758-39
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 2016
• Est. completion date: December 2025

Study information

• Verified date: August 2022
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: February 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Malignant Lymphoma

Intervention

Drug:
• PREBEN

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aarhus University Hospital	Aarhus
Denmark	Department of Hematology, Copenhagen University Hospital	Copenhagen
Denmark	Department of Hematology, Odense University Hospital	Odense
Finland	Helsinki University Hospital Comprehensive Cancer Center	Helsinki
Netherlands	Meander Medical Center	Amersfoort
Netherlands	Jeroen Bosch Hospital	Den Bosch
Netherlands	Haga Hospital, loc. Leyweg	Den Haag
Netherlands	Slingeland Hospital	Doetinchem
Netherlands	Albert Schweitzer Hospital	Dordrecht
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Spaarne Ziekenhuis	Hoofddorp
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Admiraal de Ruyter Hospital	Vlissingen
Norway	Department of Oncology, Oslo University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	Department of Oncology, St. Olavs Hospital	Trondheim
Sweden	Department of Oncology, Skåne University Hospital	Lund

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Countries where clinical trial is conducted

Denmark,  Finland,  Netherlands,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of pixantrone, bendamustine and etoposide in 'fit' relapsed aNHL pts (phase 1)		1.5 yrs
Primary	Objective ORR in both 'fit' and 'frail' relapsed aNHL pts (phase 2)		4 yrs