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Phase II Study of High-dose Methylprednisolone and Rituximab in Previously Treated Patients With High Risk Chronic B Lymphocytic Leukemia

Phase 2
18 Years
Not Enrolling
Chronic B-Lymphocytic Leukemia

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Trial Information

Phase II Study of High-dose Methylprednisolone and Rituximab in Previously Treated Patients With High Risk Chronic B Lymphocytic Leukemia

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


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


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.

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

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

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

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

End of treatment.

Safety Issue:


Principal Investigator

Laimonas Griskevicius, PhD, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vilnius University


Lithuania: Bioethics Committee

Study ID:




Start Date:

September 2007

Completion Date:

December 2009

Related Keywords:

  • Chronic B-Lymphocytic Leukemia
  • B CLL
  • Chronic B Lymphocytic Leukemia
  • Methylprednisolone
  • Rituximab
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, B-Cell