High-dose Methylprednisolone and Rituximab in High Risk B-CLL (LT-CLL-001)

February 22, 2010 updated by: Vilnius University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Lithuania
      • Klaipeda, Lithuania, 92288
        • Klaipeda Seamen's Hospital
      • Vilnius, Lithuania, 08661
        • Vilnius University Hospital Santariskiu Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab, Methylprednisolone
Drug: rituximab, methylprednisolone
Subjects will receive up-to 6 courses of IV infusion of Methylprednisolone and Rituximab every 21 day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: End of treatment.
End of treatment.

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: End of treatment.
End of treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vilnius University

Investigators

  • Principal Investigator: Laimonas Griskevicius, PhD, MD, Vilnius University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

November 13, 2007

First Submitted That Met QC Criteria

November 13, 2007

First Posted (Estimate)

November 14, 2007

Study Record Updates

Last Update Posted (Estimate)

February 23, 2010

Last Update Submitted That Met QC Criteria

February 22, 2010

Last Verified

February 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LT-CLL-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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