Efficacy and Safety Study of SH T 586 in Combination With Rituximab to Treat Low-Grade NHL

Study Overview
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Brief Summary
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The purpose of this study is to assess the antitumor effect and safety of fludarabine phosphate tablet in combination with rituximab in patient with indolent lymphoma.

Detailed Description
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As of 29 May 2009, the clinical trial sponsor is Genzyme Corporation. NOTE: This study was originally posted by sponsor Schering AG, Germany, which was subsequently renamed to Bayer Schering Pharma AG, Germany.

Official Title
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A Multicenter Study to Assess the Antitumor Effect and Safety of Fludarabine Phosphate Tablet (SH T 586) in Combination With Rituximab Administered in 6 Treatment Cycles (1 Treatment Cycle: Rituximab 375 mg/m2 iv on Day 1 Along With 5-Consecutive Day Oral Dosing of SH T 586 40 mg/m2/Day From Day 1 to Day 5, Followed by an Observation Period of 23 Days) in Patients With Indolent Lymphoma

Conditions
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Lymphoma, Low-Grade

Intervention / Treatment
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* Drug: Fludarabine Phosphate (Fludara)
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD 20 positive, relapsed/refractory indolent lymphoma. (Regimens of prior chemotherapy are limited to 2; prior rituximab treatments up to 16 times are allowed.) Patients with measurable lesions (> 1.5 cm). Patients who have not received any treatment for more than 4 weeks after completing previous therapies (6 months in the case of antibody therapies). ECOG performance status: 0 - 1 Patients with adequately maintained organ functions. Exclusion Criteria: Patients with infectious disease, serious complications, serious gastrointestinal symptoms, serious bleeding tendency, serious CNS symptoms, fever </=38 °C, interstitial pneumonia or pulmonary fibrosis, active other malignancies, autoimmune hemolytic anemia or the history of the disease, or glaucoma. Patients who are positive for HBs antigen, HCV antibody, or HIV antibody. Patients who received G-CSF or transfusion within 1 week before the registration. Patients with the history of allergies to purine nucleoside analogue. Patients who experienced serious hypersensitivity or anaphylaxis to rituximab or mouse protein-derived products. Patients who had ever received prior therapy with fludarabine phosphate injection, pentostatin, cladribine, SH T 586, blood stem cell transplant, or monoclonal antibody therapy other than rituximab to NHL (including radioimmunotherapy). Patients who had progressive disease within 6 months of receiving therapy including rituximab. Women who are pregnant, of childbearing potential, or lactating. Patients who do not agree to practice contraception.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Fludarabine Phosphate (Fludara)<br>* Injection of rituximab on Day 1 along with 5-consecutive day oral dosing of fludarabine phosphate from Day 1 to Day 5, followed by an observation period from Day 6 to Day 28 as 1 treatment cycle, 6 cycles will be given. As for patients who has been observed with partial response (PR) or better antitumor effect, any treatment shall not be provided in principle until the status comes to progressive disease (PD)<br>* Other names: BAY86-4864;|
| Active Comparator: Arm 2<br> | Drug: Rituximab<br>* Injection of rituximab on Day 1, followed by an observation period from Day 6 to Day 28 as 1 treatment cycle, 6 cycles will be given. As for patients who has been observed with partial response (PR) or better antitumor effect, any treatment shall not be provided in principle until the status comes to progressive disease (PD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | The best response until the end of 6th treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate |  | CR or CRu until the end of 6th treatment cycles | 
| Progression free survival |  | Progression or death which comes earlier, observed until 12 weeks after the completion of the treatment in the last patient | 
| Overall survival |  | Death, observed until 12 weeks after the completion of the treatment in the last patient |