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

Phase 1

Active, not recruiting

• Conditions: Malignant Lymphoma
• Interventions: Drug: PREBEN

• Registration Number: NCT02678299
• Lead Sponsor: University of Aarhus

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.

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-05
• Study First Submitted QC: 2016-02-05
• Study First Posted: 2016-02-09
• Primary Completion: 2022-02
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-03
• Last Update Posted: 2022-08-04
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	PREBEN	-

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (18)

Meander Medical Center; 🇳🇱 Amersfoort, Netherlands

Department of Oncology, Skåne University Hospital; 🇸🇪 Lund, Sweden

Department of Hematology, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Hematology, Odense University Hospital; 🇩🇰 Odense, Denmark

Department of Hematology, Copenhagen University Hospital; 🇩🇰 Copenhagen, Denmark

Albert Schweitzer Hospital; 🇳🇱 Dordrecht, Netherlands

Spaarne Ziekenhuis; 🇳🇱 Hoofddorp, Netherlands

Jeroen Bosch Hospital; 🇳🇱 Den Bosch, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Haga Hospital, loc. Leyweg; 🇳🇱 Den Haag, Netherlands

Admiraal de Ruyter Hospital; 🇳🇱 Vlissingen, Netherlands

Department of Oncology, St. Olavs Hospital; 🇳🇴 Trondheim, Norway

Helsinki University Hospital Comprehensive Cancer Center; 🇫🇮 Helsinki, Finland

Slingeland Hospital; 🇳🇱 Doetinchem, Netherlands

Medisch Spectrum Twente; 🇳🇱 Enschede, Netherlands

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

Department of Oncology, Oslo University Hospital; 🇳🇴 Oslo, Norway