Clinical trial NCT02678299: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Lymphoma
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2016-02-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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 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

Primary outcomes:
measure: MTD of pixantrone, bendamustine and etoposide in 'fit' relapsed aNHL pts (phase 1)
timeFrame: 1.5 yrs
measure: Objective ORR in both 'fit' and 'frail' relapsed aNHL pts (phase 2)
timeFrame: 4 yrs
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Hematology, Copenhagen University Hospital
city: Odense
country: Denmark
facility: Department of Hematology, Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital Comprehensive Cancer Center
city: Amersfoort
country: Netherlands
facility: Meander Medical Center
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Den Haag
country: Netherlands
facility: Haga Hospital, loc. Leyweg
city: Doetinchem
country: Netherlands
facility: Slingeland Hospital
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Vlissingen
country: Netherlands
facility: Admiraal de Ruyter Hospital
city: Oslo
country: Norway
facility: Department of Oncology, Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Trondheim
country: Norway
facility: Department of Oncology, St. Olavs Hospital
city: Lund
country: Sweden
facility: Department of Oncology, Skåne University Hospital
Study officials:
affiliation: Dept. of Hematology, Aarhus University Hospital
name: Francesco d'Amore, MD DMSci
role: PRINCIPAL_INVESTIGATOR
References: