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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Lymphoma
• Intervention / Treatment: Drug: PREBEN

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, DK-8200
    • Department of Hematology, Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Department of Hematology, Copenhagen University Hospital
  • Odense, Denmark, 5000
    • Department of Hematology, Odense University Hospital
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Hospital Comprehensive Cancer Center
• Netherlands
  • Amersfoort, Netherlands
    • Meander Medical Center
  • Den Bosch, Netherlands
    • Jeroen Bosch Hospital
  • Den Haag, Netherlands
    • Haga Hospital, loc. Leyweg
  • Doetinchem, Netherlands
    • Slingeland Hospital
  • Dordrecht, Netherlands
    • Albert Schweitzer Hospital
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen
  • Hoofddorp, Netherlands
    • Spaarne Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Vlissingen, Netherlands
    • Admiraal de Ruyter Hospital
• Norway
  • Oslo, Norway, 0310
    • Department of Oncology, Oslo University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
  • Trondheim, Norway, 7006
    • Department of Oncology, St. Olavs Hospital
• Sweden
  • Lund, Sweden, 221 85
    • Department of Oncology, Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Drug: PREBEN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Francesco d'Amore, MD DMSci, Dept. of Hematology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): February 1, 2022
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: PREBEN; 2015-000758-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No