CHAIROS Study A Study of MabThera/Rituxan (Rituximab) Maintenance Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Naive to Chemotherapy

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of intense combination treatment including MabThera/Rituxan (rituximab), followed by MabThera/Rituxan maintenance therapy in patients with B-cell CLL who are naive to chemotherapy. The anticipated time on study treatment is 2.5 years.

Official Title
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CHAIROS - Effect of Early Brief Intensification by Chemoimmunotherapy With FCR Followed by FR and Rituximab Maintenance on Clinical Response in Chemo-naïve Patients With B-CLL

Conditions
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Lymphocytic Leukemia, Chronic

Intervention / Treatment
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* Drug: rituximab [MabThera/Rituxan]
* Drug: fludarabine
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age B-cell CLL No previous chemotherapy, radiotherapy, or immunotherapy Exclusion Criteria: Reduced organ function, or bone marrow dysfunction not due to CLL Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer Patients with a history of severe cardiac disease.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MabThera/Rituxan<br> | Drug: rituximab [MabThera/Rituxan]<br>* Every 4 weeks for 6 cycles of induction, followed by maintenance therapy every 3 months x 8<br>Drug: fludarabine<br>* Every 4 weeks, 6 cycles<br>Drug: cyclophosphamide<br>* Every 4 weeks, 3 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) | Best clinical response was determined according to the National Cancer Institute (NCI) Clinical and Clinical plus (+) Radiological evaluations by central response assessment. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of chronic lymphocytic lymphoma (CLL) with additional computerized tomography (CT) scan evaluation of lymphadenopathy. Per NCI guidelines, CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils greater than (>)1500 per microliter (/µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 grams per deciliter (g/dL), lymphocytes (LC) (less than) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC. | Weeks 1, 5, 9, 12, 13, 17, 21 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) | Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, partial remission (PR), partial remission with toxicity associated (PRTox), progressive disease (PD), and stable disease (SD) were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). Last observation carried forward (LOCF) method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum. | Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose) | 
| Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) | Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, PR, PRTox, PD, and SD were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). LOCF method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum. | Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose) | 
| Time to Next Treatment - Percentage of Participants With an Event | Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment. | Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months | 
| Time to Next Treatment - Time to Event | Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment. | Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months | 
| Percentage of Participants With Adverse Events (AEs) | AEs were recorded from the date of first medication administration until 28 days after the last trial medication. | Day 1 of Cycles 1, 2, 3, 4, 5, and 6 to 28 days after the last trial medication. |