Main info

Identifier:

HO144 NHL

Sponsor:

Aarhus University Hospital

Working group party:

Lymphoma

Age:

18-85

Stage:

2nd Line

Echelon:

Level D

Included patients:

4

(of 30)

Active sites:

9

(of 10)

1 sites are pending

Title:

A phase 1/2 study of combination therapy with pixantrone , (rituximab for CD20 positive tumours), etoposide and bendamustine in patients with relapsed aggressive lymphoma of B or T cell phenotype – P[R]EBEN.

Timeline

Flow

Details

Phase:

Prospective Phase I/II study

Monitoring Type:

Not any more

Objectives:

Primary Objectives

• Determine the MTD of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in ‘fit' patients with rel aNHL of B- or T-cell phenotype.
• Evaluate the ORR and PFS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine either at the identified MTD (P[R]EBEN-fit) in ‘fit’ patients or at the baseline dose level (P[R]EBEN-frail) in ‘frail’ patients with rel aNHL.

Secondary objectives

• Evaluate the CR, PR, duration of response, and OS using the combination of pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with Bor T-cell NHL.
• Evaluate the safety and tolerability of combination therapy with pixantrone, rituximab (only in CD20 positive tumors), etoposide, and bendamustine in patients with aggressive B- or T-cell NHL.
• To perform molecular analyses at nucleic acid (DNA, RNA, microRNA) and protein level to see if specific molecular features can predict responder versus non-responder status.

Eligibility

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 performance score (PS) 0-1 at protocol entry (for ECOG definition see appendix A)
  • 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 (for ECOG definition see appendix A), and/or
  • Deemed ‘frail’ by the treating physician
• At least 6 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) (can be post transfusion)
• Platelets ≥ 100 x 10^9/L; ≥ 75 x10^9/ permitted if bone marrow involvement
• Absolute neutrophil count ≥ 1.5 x 10^9/L; ≥ 1.0 x 10^9/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 ULN
• 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

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals