HOVON HO144 NHL
- HO144 NHL
- Working group party:
- 2nd Line
- Level D
- Included patients:
- Active sites:
9(of 10)1 sites are pending
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.
- Prospective Phase I/II study
- Monitoring Type:
- Site Evaluation Visit
- 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.
- 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.
- 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
Patients should be registered using a study specific patient registration form at the CTO:
Helle Erbs Toldbod
Department of Hematology, A-CTO
Palle Juul-Jensens Boulevard 99
DK-8200 Aarhus N
Tel.: +45 7845 5855
The following information will be registered at study entry:
- Institution name
- Name of responsible investigator
- Date of birth
- Date of primary lymphoma diagnosis
- Histological lymphoma subtype at primary diagnosis
- Date of present histologically confirmed relapse
- Histological lymphoma subtype at present relapse
- Eligibility criteria (i.e. all inclusion and exclusion criteria)
Each patient will be given a unique patient study number by the CTO. For phase 1 patients, the CTO will inform the site of which dose level to apply.
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