Identifying Prognostic Factors in Frontline FCR for Patients With Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn more about the characteristics of CLL, including genes and chromosome abnormalities and proteins expressed by the leukemia cells, which may help doctors predict if patients who receive standard treatment (fludarabine, cyclophosphamide, and rituximab) for the first time will experience a complete remission.

Detailed Description
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The Study Drugs: Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying. Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. Rituximab is designed to attach to lymphoma cells, which may cause them to die. Study Drug Administration: Each cycle is 4-6 weeks. If you are found to be eligible to take part in this study, on Day 1 of each cycle, you will receive rituximab through a needle into your vein over 6-8 hours. On Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond, you will receive fludarabine by vein over 30 minutes. You will also receive cyclophosphamide by vein over 30 minutes. You will receive drugs (such as Tylenol, Benadryl, Zofran, allopurinol, and Valtrex) to help prevent side effects. If you have side effects while receiving rituximab, you may be monitored by the study staff for 2 hours after each dose. Study Visits: Once a week, blood (about 1 tablespoon) will be drawn for routine tests. After 3 months (3 cycles of treatment), the following tests and procedures will be performed: You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests. You will have a bone marrow aspirate and biopsy to check the status of the disease. Length of Study: You will be on treatment for about 6 months. You will be taken off treatment early if you have intolerable side effects or the disease gets worse. End-of-Treatment Visit: After you are off treatment, you will have an end-of-treatment visit for doctors to learn your overall response to the treatment. The following tests and procedures will be performed: You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests. You will have a bone marrow aspirate and biopsy to check the status of the disease. Long-Term Follow-up: At 6 months after you have finished treatment and then every year from then on, you will have follow-up visits. The following tests and procedures will be performed: You will have a physical exam. Blood (about 2 tablespoons) will be drawn for routine tests. If your doctor thinks it is needed, you will have a bone marrow biopsy and aspirate to check the status of the disease. This is an investigational study. Fludarabine, cyclophosphamide, and rituximab are FDA approved and commercially available for the treatment of CLL. The correlation with response to treatment and the characteristics of the leukemia cells is investigational. Up to 300 patients will take part in this study. All will be enrolled at MD Anderson.

Official Title
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Prospective Identification of Significant Prognostic Factors in Patients Treated With Fludarabine, Cyclophosphamide, and Rituximab (FCR) as Initial Therapy for Chronic Lymphocytic Leukemia.

Conditions
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Chronic Lymphocytic Leukemia, Leukemia

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will have a diagnosis of CLL, Small Lymphocytic Lymphoma (SLL), or CD20 positive low-grade lymphoproliferative disorder. All patients with untreated Rai stage III-IV are eligible for this protocol. Prior treatment with single-agent rituximab permitted. OR Patients with untreated Rai stage 0-II who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL). Prior treatment with single-agent rituximab permitted. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Patients must have adequate renal and hepatic function (creatinine <2mg%, bilirubin <2mg%). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman. Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply. Patients must be 16 years of age or older. Patients must sign informed consent indicating that they are aware of the investigational nature of this study according to the policies of the MD Anderson Cancer Center Institutional Review Board (MDACC IRB). Exclusion Criteria: N/A

Ages Eligible for Study
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Minimum Age: 16 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: Fludarabine, Cyclophosphamide, Rituximab<br>Fludarabine 25 mg/m^2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond. Cyclophosphamide 250 mg/m2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond. Rituximab 375 mg/m2 given intravenously on Day 1 of Course 1 All subsequent Courses: 500 mg/m2 given intravenously on Day 1 (Weeks 5,9,13,17,21) | Drug: Fludarabine<br>* 25 mg/m^2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond.<br>* Other names: Fludara®;Drug: Cyclophosphamide<br>* 250 mg/m2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond.<br>* Other names: Neosar®;Drug: Rituximab<br>* 375 mg/m2 given intravenously on Day 1 of Course 1 All subsequent Courses: 500 mg/m2 given intravenously on Day 1 (Weeks 5,9,13,17,21)<br>* Other names: Rituxan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Remission (CR) | Complete Response defined by NCI Working Group / International Working Group for CLL criteria as no evidence of disease on physical examination (no adenopathy or organomegaly) or microscopic examination of blood (ALC <4,000/L) and bone marrow (<30% lymphocytes, no lymphoid nodules), and recovery of hemoglobin, neutrophil, and platelet counts. | After 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia, Leukemia, FCR, Fludarabine, Cyclophosphamide, Rituximab