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

Wolfson Medical Center (WMC)

Status and phase

Unknown

Phase 2

Conditions

Advanced Refractory Chronic Lymphocytic Leukemia

Treatments

Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)

Study type

Interventional

Funder types

Other

Identifiers

NCT00892827

AK- 01

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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