Fludarabine, Pixantrone and Rituximab vs Fludarabine and Rituximab forRelapsed or Refractory Indolent 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 reduced delayed cardiotoxicity in animal models compared to reference standards. This cytotoxic agent has structural similarities to mitoxantrone as well as general similarities to anthracyclines (such as the tricyclic central quinoid chromophore7). This phase III study will compare the efficacy and safety of the combination BBR 2778, fludarabine, and rituximab with the combination fludarabine and rituximab in patients with relapsed or refractory indolent non-Hodgkin's lymphoma.

Official Title
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Fludarabine, BBR 2778 (Pixantrone) and Rituximab (FP-R) vs Fludarabine and Rituximab (F-R) for Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: fludarabine and rituximab
* Drug: fludarabine, rituximab, pixantrone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically confirmed relapsed or refractory indolent non-Hodgkin's lymphoma (NHL) Any stage (Ann Arbor staging, Appendix 15.7), with or without B symptoms CD 20+ lymphoma (confirmed by immunochemistry) Measurable disease. Atleast 1 prior therapy. Age ≥ 18 years Life expectancy of at least 3 months ECOG performance status (PS) of 0 or 1 Adequate cardiac function defined as LVEF ≥ 50% by MUGA scan Adequate renal function Adequate hepatic function Adequate bone marrow function Recovery from all acute toxicities from prior therapies (except alopecia and grade 1 peripheral neuropathy). Exclusion Criteria Prior treatment with a cumulative dose of doxorubicin equivalent exceeding 450 mg/m2 Radiotherapy, chemotherapy or other therapies for NHL within 4 weeks of treatment start Systemic corticosteroids to treat NHL within 5 days prior to first dose of study treatment. Radioimmunotherapy (RIT) within 3 months of treatment start Known hypersensitivity to the excipients or the study drugs that the patient will receive Known Type I hypersensitivity or anaphylactic reactions to murine proteins or to any component of rituximab Major thoracic and/or abdominal surgery in the preceding 4 weeks, from which the patient has not fully recovered (patients who have had minor surgery and one week's recovery period may be enrolled) HIV-related lymphoma Active CNS involvement Clinically significant cardiovascular abnormalities Serious (NCI CTCAE grade 3-4) intercurrent infection at randomization, infection requiring oral antibiotics, or deep-seated or systemic mycotic infections. Investigational study drug within 30 days before randomization. Patient must have recovered from all side effects of other investigational therapy. Clinical symptoms suggesting unresolved HIV, HBV or HCV infection. . History of another malignancy except: curatively treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in remission, or any other cancer from which the patient has been disease-free for 5 years Pregnant or lactating women Potentially fertile men and women and their sexual partners not willing to use adequate contraception as defined by the Investigator during the study and for 6 months after the last day of study drug administration

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Comparator<br>fludarabine and rituximab | Drug: fludarabine and rituximab<br>* days 1 to 4 of six 28-day cycles rituximab 375 mg/m2 fludarabine 25 mg/m2<br>|
| Experimental: Experimental<br>fludarabine, rituximab, pixantrone | Drug: fludarabine, rituximab, pixantrone<br>* days 1 to 4 of six 28-day cycles rituximab 375 mg/m2 fludarabine 25 mg/m2 pixantrone 120 mg/m2 day 2 only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | day 64-71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate, survival, safety |  | every 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, pixantrone, rituximab, fludarabine