High-Dose Methylprednisolone and Rituximab in High Risk B-CLL
Information source: Vilnius University
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic B-Lymphocytic Leukemia
Intervention: rituximab, methylprednisolone (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Vilnius University Official(s) and/or principal investigator(s):
Laimonas Griskevicius, PhD, MD, Principal Investigator, Affiliation: Vilnius University
Overall contact:
Laimonas Giskevicius, PhD, MD, Phone: 0037052365029, Email: laimonas.griskevicius@santa.lt
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 characterize the safety profile of
high-dose Methylprednisolone and Rituximab.
Clinical Details
Official title: Phase II Study of High-Dose Methylprednisolone and Rituximab in Previously Treated Patients With High Risk Chronic B Lymphocytic Leukemia
Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Primary outcome: Primary endpoint will be the ORR defined as the proportion of patients achieving CR, CR with MRD negativity (Complete Flow Cytometric Remission), nPR and PR.
Secondary outcome: PFS defined as time from the first day of treatment to the day the subject progresses or dies of any cause.
OS defined as time from the first day of treatment to the day the subject dies of any cause.
Detailed description:
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 characterize the safety profile of
high-dose Methylprednisolone and Rituximab.
Patient Population Patients with previously treated symptomatic high risk B-CLL 18 years of
age and older.
Study Duration The study period for each subject is expected to be 21 months. Subjects will
receive up-to 6 cycles of IV infusion of Methylprednisolone and Rituximab. Maximum duration
of treatment is expected to be 9 months. All infusions of study treatment will be
administered by medically qualified site staff in an inpatient or outpatient clinic under the
supervision of an Investigator. Subjects will complete scheduled visits not later than Study
Month 21, after which time 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, except in cases lost to follow up, or if a subject withdraws informed
consent.
Study Design Phase II, multicenter, non-randomized, open label study.
Maximum Recruitment Period 2 years
Number of Planned Subjects Approximately 50 patients.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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:
1. 1. Weight loss more 10 percent within the previous 6 months; 1. 2. Fatigue (e. g. WHO
performance status 2 or more); 1. 3. Fever 38C or more 2 weeks or more without evidence
of infection; 1. 4. Night sweats without evidence of infection.
2. Evidence of progressive marrow failure as manifested by:
2. 1. anemia (less 110 g/l) and / or 2. 2. thrombocytopenia (less 100 x 109/l) within
the previous 6 months and / or 2. 3. 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
4. High-risk B-CLL biologically or clinically: 4. 1. Biologically high-risk B-CLL is defined
by the presence of at least one of the following factors: 4. 1.1. 98 percent or more lgVH
genes are homologous to the embryonic sequence and / or 4. 1.2. 17p del confirmed by FISH
or 4. 1.3. 11q del confirmed by FISH or 4. 1.4. 12 trisomy. 4. 2. Clinically high-risk B-CLL
is defined by the presence of at least one of the following factors: 4. 2.1. Progressive or
stable disease while on Fludarabine treatment. 4. 2.2. Relapse after Fludarabine treatment
within 12 months. 5. Older than 18 years. 6. 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.
Locations and Contacts
Laimonas Giskevicius, PhD, MD, Phone: 0037052365029, Email: laimonas.griskevicius@santa.lt
Klaipeda Seamen's Hospital, Klaipeda 92288, Lithuania; Recruiting
Romualdas Jurgutis, PhD, MD, Phone: +37068534913, Email: mjurgutis@takas.lt
Mindaugas Jurgutis, MD, Sub-Investigator
Vilnius University Hospital Santariskiu Clinics, Vilnius 08661, Lithuania; Recruiting
Laimonas Griskevicius, PhD, MD, Phone: +370 5 2365 029, Email: laimonas.griskevicius@santa.lt
Laimonas Griskevicius, PhD, MD, Principal Investigator
Additional Information
Starting date: September 2007
Ending date: September 2009
Last updated: September 12, 2008
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