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

University of Aarhus

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Malignant Lymphoma

Treatments

Drug: PREBEN

Study type

Interventional

Funder types

Other

Identifiers

NCT02678299

PREBEN

2015-000758-39 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

Enrollment

60 patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

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