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 Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment
|
Drug: PREBEN
|
Outcome Measures
Primary Outcome Measures
- 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]
Eligibility Criteria
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
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Vaccination with live, attenuated vaccines within 4 weeks of inclusion
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Pregnant and/or breastfeeding women
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology, Aarhus University Hospital | Aarhus | Denmark | DK-8200 | |
| 2 | Department of Hematology, Copenhagen University Hospital | Copenhagen | Denmark | 2100 | |
| 3 | Department of Hematology, Odense University Hospital | Odense | Denmark | 5000 | |
| 4 | Helsinki University Hospital Comprehensive Cancer Center | Helsinki | Finland | 00029 | |
| 5 | Meander Medical Center | Amersfoort | Netherlands | ||
| 6 | Jeroen Bosch Hospital | Den Bosch | Netherlands | ||
| 7 | Haga Hospital, loc. Leyweg | Den Haag | Netherlands | ||
| 8 | Slingeland Hospital | Doetinchem | Netherlands | ||
| 9 | Albert Schweitzer Hospital | Dordrecht | Netherlands | ||
| 10 | Medisch Spectrum Twente | Enschede | Netherlands | ||
| 11 | Universitair Medisch Centrum Groningen | Groningen | Netherlands | ||
| 12 | Spaarne Ziekenhuis | Hoofddorp | Netherlands | ||
| 13 | Erasmus Medical Center | Rotterdam | Netherlands | ||
| 14 | Admiraal de Ruyter Hospital | Vlissingen | Netherlands | ||
| 15 | Department of Oncology, Oslo University Hospital | Oslo | Norway | 0310 | |
| 16 | Stavanger University Hospital | Stavanger | Norway | ||
| 17 | Department of Oncology, St. Olavs Hospital | Trondheim | Norway | 7006 | |
| 18 | Department of Oncology, Skåne University Hospital | Lund | Sweden | 221 85 |
Sponsors and Collaborators
- University of Aarhus
Investigators
- Principal Investigator: Francesco d'Amore, MD DMSci, Dept. of Hematology, Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PREBEN
- 2015-000758-39