BBR 2778 for Relapsed, Aggressive Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and shows reduced potential for cardiotoxicity in animal models. This cytotoxic agent has structural similarities with mitoxantrone as well as general similarities with anthracyclines (such as the tricyclic central quinoid chromophore).

Detailed Description
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The primary study objective is to compare the efficacy of BBR 2778 to a selection of single agents. Secondary objectives are to compare the safety and tolerability of BBR 2778 to a selection of single agents, and to assess the pharmacokinetic parameters of BBR 2778 in a subset of this patient population.

Official Title
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Pixantrone (BBR 2778) Versus Other Chemotherapeutic Agents for Third-line Single Agent Treatment of Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma: A Randomized, Controlled, Phase III Comparative Trial

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone
* Drug: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed aggressive [de novo or transformed] NHL according to REAL/WHO classification. At least one objectively measurable lesion as demonstrated by CT, spiral CT, or MRI and plain radiograph of the chest (chest x-ray, for chest lesions only) that can be followed for response as target lesion. Relapse after 2 or more prior regimens of chemotherapy ECOG performance status of 0, 1, or 2 Adequate hematologic, renal and hepatic function LVEF ≥50% determined by MUGA scan Exclusion Criteria: Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m² Prior allogenic stem cell transplant Histological diagnosis of Burkitt lymphoma, lymphoblastic lymphoma or Mantle cell lymphoma Active CNS lymphoma or HIV-related lymphoma. Any chemotherapy, radiotherapy, or other anticancer treatment (including corticosteroid, 10 or more mg/day of prednisone or equivalent) within the 2 weeks before randomization Pregnant women or nursing mothers

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Pixantrone (BBR2778) | Drug: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone<br>* Day 1: pixantrone (150 mg/m2), cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day)<br>* Other names: BBR2778;|
| Active Comparator: Comparator Arm<br>To be chosen by the investigator, among vinorelbine, oxaliplatin, ifosfamide, etoposide or mitoxantrone | Drug: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab<br>* Day 1: cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) and Complete Response Unconfirmed (CRu) | Proportion of patients with a best response of complete response (CR) or Complete Response unconfirmed (CRu) in the End Of Treatment (EOT) or End Of Study (EOS) analyses by independent assessment in the Intent-to-treat (ITT) population through the End of Treatment (EOT) | EOT; approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | The time between the date of randomization and the date of the initial documentation of progressive/relapsed disease or death due to any cause. | 18 months after 6 cycles of treatment; approximately 24 months | 
| Overall Survival | The time between the date of randomization and the date of death due to any cause. | 18 months after 6 cycles of treatment; approximately 24 months | 
| Overall Response Rate (ORR) Lasting at Least 4 Months | The proportion of patients with Complete response or Partial Response with a difference from the first documented objective response to disease progression or death of at least 4 months. | approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pixantrone, Non-Hodgkins lymphoma