Rituximab in Pretreated Elderly or Unfit B-CLL Patients

Study Overview
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Brief Summary
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The study will test the efficacy rituximab in addition to glucocorticoids for the treatment of B-CLL in elderly or unfit patients.

Detailed Description
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Patient Population: Pretreated patients with symptomatic B-CLL 18-64 years of age with poor performance status or >/=65 years of age with any performance status. Treatment: Up-to 4 cycles of glucocorticoid (Methylprednisolone or Dexamethasone) and Rituximab every 21 day. Study Duration: The study period for each subject is expected to be 21 months. Subjects will receive up-to 4 cycles of IV infusion of Rituximab and Glucocorticoid. Maximum duration of treatment is expected to be 6 months. Subjects will complete scheduled visits not later than Study Month 21, thereafter they will enter into the long-term follow-up period. Subjects will be followed every 3 months for disease progression, initiation of subsequent leukemia treatment or survival.

Official Title
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Study of Rituximab in Addition to Glucocorticoid in Pretreated Elderly or Unfit Patients With Chronic B Lymphocytic Leukemia

Conditions
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B-Cell Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Rituximab
* Drug: Glucocorticoid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of CD20 positive chronic B lymphocytic leukemia (BCLL) confirmed by biopsy or flow-cytometry. Previously treated patients with stage Rai I-IV and progressive disease (according to IWCLL 2008 guidelines). Active B-CLL is defined by at least one of the following: At least one of the disease related symptoms: Constitutional symptoms: Weight loss >10% within the previous 6 months; Fatigue (e.g., WHO performance status >/=2); Fever >/=38C >/=2 weeks without evidence of infection; Night sweats for more than 1 month without evidence of infection. Evidence of progressive marrow failure as manifested by development of, or worsening of, anemia and/or thrombocytopenia Autoimmune hemolysis and/or thrombocytopenia poorly responsive to corticosteroid therapy. Massive (i.e., >/=6 cm bellow left costal margin) or progressive or symptomatic splenomegaly. Massive lymphadenopathy or conglomerates (i.e., >/=10 cm in largest diameter) or progressive or symptomatic lymphadenopathy. Progressive lymphocytosis with an increase >50% over a 2-month period or an anticipated doubling time of less than 6 months. In patients with initial blood lymphocyte counts of less than 30x10^9/L LDT should not be used as a single parameter to define treatment indication. Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for protocol therapy. Either of the following: 18 years of age or older with impaired performance status (CIRS > 6) and /or 65 years of age or older with any performance status. Signed informed consent form. Exclusion Criteria: Intolerance to exogenous protein or known severe reaction to the administration of Rituximab. Active infection. Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study Day 1. TBC or fungal infection within the past 6 months even if adequately controlled by treatment. Severe organ deficiency preventing the participation in the study. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1. Active peptic ulcer. Inadequately controlled diabetes mellitus. Suspected or confirmed B-CLL CNS disease. Known to be HIV positive. Difficult to control, uncooperative patients. Allergic disorders in need of chronic glucocorticoid therapy. Other oncological diseases requiring active treatment (except hormonal therapy). Pregnancy and breastfeeding. Patients of reproductive potential who are not using effective methods of contraception.

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: R-HDMP<br>Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4). Glucocorticoid (either Dexamethasone or Methyl-prednisolone) infusions will be administered on Days 1 to 3 (cycles 1-4(6)) and should precede the Rituximab infusion. | Drug: Rituximab<br>* Rituximab (Rtx) antibody infusions will be administered on Day 1, 2, 3 (cycle 1) and Day 1 (cycles 2 to 4).<br>* Other names: MabThera;Drug: Glucocorticoid<br>* Glucocorticoid (either Dexamethasone or Methyl-prednisolone) infusions will be administered on Days 1 to 3 (cycles 1-4(6)) and should precede the Rituximab infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate (ORR) is defined according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL 2008) guidelines, as the proportion of patients achieving complete response (CR), CR with minimal residual disease (MRD) negativity (complete molecular remission), nodular partial remission (nPR) and partial response (PR). | 3 months +/- 2 weeks after the last treatment cycle. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival (PFS) will be defined as the interval from entry into the study to disease progression or death. | up to 12 months | 
| Number of Participants With Adverse Events | Adverse events NCI CTCAE, version 4.0. Hematological toxicity was evaluated according to IWCLL 2008 guidelines. | 6 months. | 
| Overall Survival | Overall survival (OS) will be defined as the interval from date of randomization until the date of death from any cause, assessed up to 100 months. | from date of randomization until the date of death from any cause, assessed up to 100 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic lymphocytic leukemia, relapsed, elderly or unfit patients, methylprednisolone, rituximab