Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia

September 12, 2010 updated by: Wolfson Medical Center

The Efficacy and Safety of Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia. Single-arm Phase II Study. Analysis of Complement Activation Pathways.

Chronic lymphocytic leukemia (CLL), an indolent disease of mature-looking B lymphocytes, is the most common leukemia in Israel and the Western world. The disease is associated with considerable morbidity and mortality, and is currently incurable. Rituximab (Mabthera) is a chimeric monoclonal antibody directed against CD20 antigen, present exclusively on B lymphocytes. Treatment with Rituximab is widely used in indolent B cell malignancies. However, the administration of Rituximab in CLL patients yields less successful results than in other indolent B cell malignancies, and even responding patients may become refractory. We hypothesized that the abnormalities in the complement system identified in CLL underlie the suboptimal response to Rituximab, since complement-dependent cell cytotoxicity is a major mechanism of Rituximab action. Following patient consent and Institutional Review Board approval, standard-dose Rituximab (375 mg/m2) will be administered, preceded by 2 units of FFP. This treatment will be repeated every 1-2 weeks for 4-6 cycles. The clinical and laboratory parameters, as well as adverse drug events, will be monitored.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Indolent B cell Non-Hodgkin's lymphoma patients show good responses to Rituximab, administered either alone or preferably with standard chemotherapy. The response to Rituximab of patients with CLL is inferior in comparison to other indolent B cell malignancies. The therapeutic approach of combining treatments with Rituximab and fresh frozen plasma (FFP) used by us first in one case and following the impressive response - in additional 2 patients, was undertaken on the basis of two observations.

We assumed, that the addition of FFP to Rituximab treatment would increase and/or restore the efficacy of Rituximab in advanced CLL patients that are resistant to therapy by correcting their abnormal complement system thus allowing improved complement activation and increase anti-leukemic activity.

The major aims of the study are: (1) To establish the efficacy of the combination of FFP and RTX as determined by response rate. (2) To elucidate the effector mechanism responsible for the efficacy of the FFP-Rituximab combination. The secondary aims of the study are (1) To establish the response duration of the combination of FFP and RTX as determined by time to progression. and time to re treatment (2) To determine the safety of the combined treatment.

The study is designed as a single-arm, phase II study evaluating the efficacy and safety of combined treatment with FFP and RTX in advanced refractory chronic lymphocytic leukemia, along with an analysis of the complement system associated parameters.

Study Type

Interventional

Enrollment (Anticipated)

10

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

  • Israel
      • Holon, Israel, 58100
        • Recruiting
        • Wolfson MC
        • Contact:
        • Sub-Investigator:
          • Goldstein Daniela, MD
        • Sub-Investigator:
          • Gil Lugassy, Prof.
        • Sub-Investigator:
          • Ami Schattner, Prof.

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:

  • Diagnosis: advanced (Rai stage ≥2 or symptomatic stage 1) CLL Resistant to or relapsing after treatment with Fludarabine and/or Rituximab
  • Lymphocyte count of 100,000 cells/mcl or higher.
  • Time from last anti-leukemia treatment: 1 month or more
  • Age: male or female over 18 years of age.
  • Informed consent - obtained

Exclusion Criteria:

  • Lack of one or more of the inclusion criteria
  • Known sensitivity to human plasma
  • Known sensitivity to Rituximab (Mabthera)
  • Active second malignant disease (other than non-melanoma skin cancer) < 2 years prior to the study
  • Active infectious disease < 1 month prior to the study
  • Hepatitis B serology: Hepatitis B surface antigen - positive
  • Renal function: Creatinin > 3 mg/dL
  • Liver function: Liver enzymes less than x2 of the normal values
  • Performance status: ECOG performance status 4
  • Use of other investigational agent < 30 days ago
  • Known poor adherence to treatment plan

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm Study
Rituximab
Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)
Rituximab (375 mg/m2) with FFP will be given every two weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To establish the efficacy of the combination of FFP and RTX as determined by response rate. Complete/Partial Response includes parameters: Physical Exam,Symptoms,Lymphocytes, Neutrophils, Platelets,Hb (g/dL),Bone marrow lymph
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to disease progression
Time Frame: 6-12 months
6-12 months
Time to re-treatment
Time Frame: 6-12 months
6-12 months
Safety of the combination treatment of FFP and RTX
Time Frame: 6-12 months
6-12 months

Collaborators and Investigators

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

Sponsor

Wolfson Medical Center

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

April 1, 2009

Primary Completion (Anticipated)

July 1, 2009

Study Completion (Anticipated)

December 1, 2010

Study Registration Dates

First Submitted

May 4, 2009

First Submitted That Met QC Criteria

May 4, 2009

First Posted (Estimate)

May 5, 2009

Study Record Updates

Last Update Posted (Estimate)

September 14, 2010

Last Update Submitted That Met QC Criteria

September 12, 2010

Last Verified

September 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AK- 01

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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