Comparative Trial for Pixantrone in Combination With Rituximab in Indolent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether combining pixantrone (BBR 2778, INN name pending) with the monoclonal antibody rituximab, leads to an increase in the period of patients' remission, compared to rituximab alone.

Detailed Description
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This trial is being conducted in patients with indolent (or low-grade) non-Hodgkin's lymphoma, who have either relapsed or been refractory to previous treatment. Pixantrone belongs to the DNA intercalator family of chemotherapy agents, which includes anthracyclines. DNA intercalators are commonly used to treat patients with indolent NHL, often in combination with the monoclonal antibody rituximab. This study represents the first large-scale, comparative trial in indolent NHL, designed to determine whether the response rate and time to tumour progression in patients treated with a combination of rituximab and a DNA intercalator, is significantly higher than seen in patients treated with rituximab alone. This trial is randomized and controlled, which means that participating patients will be randomly assigned to one of two treatment groups: Patients treated with both pixantrone and rituximab, in combination Patients treated with only rituximab This trial is expected to recruit around 800 patients in the US, Europe and Israel, with 400 patients recruited to each group. Patients will be treated for around 18 weeks and will recieve regular physician monitoring for five years from the end of treatment.

Official Title
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An Open-Label, Randomized, Phase III Comparative Trial of BBR 2778 + Rituximab Versus Rituximab in the Treatment of Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma (NHL)

Conditions
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Lymphoma, Follicular, Lymphoma, Mixed-Cell, Follicular, Lymphoma, Small Cleaved-Cell, Follicular, Lymphoma, Low-Grade

Intervention / Treatment
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* Drug: rituximab
* Drug: Pixantrone (BBR 2778)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL), including follicular lymphoma grade I and II Presenting with an episode of progressive disease, following 1-5 prior treatments (with either radiation, chemotherapy or rituximab). Exclusion criteria: Patients that failed to respond to previous rituximab treatment, or relapsed within 6 months of the first rituximab infusion Patients known to have an allergic reaction to rituximab or murine derived proteins.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: rituximab|nan|
|Drug: Pixantrone (BBR 2778)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the time to tumor progression (TTP) of the combination of BBR 2778 (pixantrone) + rituximab with that of rituximab alone |  | For 5 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare BBR 2778 + rituximab versus rituximab for: | objective overall response rate (ORR; CR + PR) objective complete response rate (CRR) rate of molecular remission time to response time to complete response duration of response Time to Tumor Progression requiring treatment Quality-Adjusted Time To Progression (QATTP) overall survival disease-specific survival safety/tolerability | For 5 years post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pixantrone, BBR 2778, chemotherapy, DNA Intercalator, Anthracycline, Rituximab, Rituxan, Mabthera, monoclonal antibody, antibody, NHL, Non-Hodgkin's lymphoma, indolent, low grade, Novuspharma