High-dose Methylprednisolone and Rituximab in High Risk B-CLL

Launched by VILNIUS UNIVERSITY · Nov 13, 2007

Keywords

ClinConnect Summary

Studies have shown that both high-dose Methylprednisolone and Rituximab used as single agents are effective in relapsed and refractory B-CLL. Methylprednisolone acts independently of p53 apoptosis pathway. The combination of both drugs may improve response and outcome in previously treated high-risk B-CLL patients.

Study Objectives

Primary:

To determine the clinical benefit of high-dose Methylprednisolone and Rituximab in previously treated high-risk B-CLL patients in terms of clinical and flowcytometric response rate.

Secondary:

To determine progression free and overall survival. To c...

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Eligibility criteria

• Inclusion Criteria:
• • 1. The diagnosis of CD20 positive chronic B lymphocytic leukemia (B-CLL) confirmed by biopsy or flow-cytometry.
• • 2. Relapsed or progressive disease after at least 1 prior chemotherapy.
• • 3. Stage Rai I-IV and progressive disease (according to NCI criteria). NCI progressive disease criteria16
• Active B-CLL is defined by at least one of the following:
• At least one of the disease related symptoms:
• 1. Constitutional symptoms:
• • Weight loss more 10 percent within the previous 6 months;
• • Fatigue (e. g. WHO performance status 2 or more);
• • Fever 38C or more 2 weeks or more without evidence of infection;
• • Night sweats without evidence of infection.
• 2. Evidence of progressive marrow failure as manifested by:
• • anemia (less 110 g/l) and / or
• • thrombocytopenia (less 100 x 109/l) within the previous 6 months and / or
• • neutropenia (less 1 x 109/l) within the previous 6 months.
• • 3. Autoimmune hemolysis and / or thrombocytopenia poorly responsive to corticosteroid therapy.
• • 4. Massive (i. e.6 cm or more bellow left costal margin) or progressive splenomegaly with progressive increase on 2 consecutive visits at least 2 weeks apart.
• • 5. Massive lymphadenopathy or conglomerates (i.e., 10 cm or more in largest diameter) or progressive lymphadenopathy with increase on 2 consecutive visits at least 2 weeks apart.
• • 6. Progressive lymphocytosis with an increase more 50 percent over a 2-month period or an anticipated doubling time of less than 6 months.
• • 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
• 1. High-risk B-CLL biologically or clinically:
• * Biologically high-risk B-CLL is defined by the presence of at least one of the following factors:
• • 98 percent or more lgVH genes are homologous to the embryonic sequence and / or
• • 17p del confirmed by FISH or
• • 11q del confirmed by FISH or
• • 12 trisomy.
• * Clinically high-risk B-CLL is defined by the presence of at least one of the following factors:
• • Progressive or stable disease while on Fludarabine treatment.
• • Relapse after Fludarabine treatment within 12 months.
• • Older than 18 years.
• • Signed informed consent form.
• Exclusion Criteria:
• • 1. Intolerance to exogenous protein or known severe reaction to the administration of Rituximab.
• • 2. Active infection.
• • 3. Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study Day 1.
• • 4. TBC or fungal infection within the past 6 months even if adequately controlled by treatment.
• • 5. Severe organ deficiency preventing the participation in the study.
• • 6. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.
• • 7. Severe liver disease (total bilirubin or transaminases more 3 times ULN), except caused by the B-CLL.
• • 8. Active peptic ulcer.
• • 9. Inadequately controlled diabetes mellitus.
• • 10. Suspected or confirmed B-CLL CNS disease.
• • 11. Known to be HIV positive.
• • 12. Difficult to control, uncooperative patients.
• • 13. Allergic disorders in need of chronic glucocorticoid therapy.
• • 14. Other oncological diseases requiring active treatment (except hormonal therapy).
• • 15. Pregnancy and breastfeeding.
• • 16. Patients of reproductive potential who are not using effective methods of contraception.