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

NCT ID: NCT00892827

Last Updated: 2010-09-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2010-12-31

Brief Summary

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.

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.

Conditions

Advanced Refractory Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm Study

Rituximab

Group Type: EXPERIMENTAL

Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)

Intervention Type: DRUG

Rituximab (375 mg/m2) with FFP will be given every two weeks

Interventions

Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)

Rituximab (375 mg/m2) with FFP will be given every two weeks

Intervention Type: DRUG

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wolfson Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Wolfson Medical Center, Holon, Israel

Locations

Wolfson MC

Holon, Holon, Israel

Site Status: RECRUITING

Countries

Israel

Facility Contacts

Abraham Klepfish, MD

Role: primary

klepfish@wolfson.health.gov.il

972-35028778

Other Identifiers

AK- 01

Identifier Type: -

Identifier Source: org_study_id