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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Wolfson Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Wolfson Medical Center
ClinicalTrials.gov Identifier:
NCT00892827
First received: May 4, 2009
Last updated: September 12, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Advanced Refractory Chronic Lymphocytic Leukemia
Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Wolfson Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: 6-12 months ] [ Designated as safety issue: Yes ]
  • Time to re-treatment [ Time Frame: 6-12 months ] [ Designated as safety issue: Yes ]
  • Safety of the combination treatment of FFP and RTX [ Time Frame: 6-12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: April 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Study
Rituximab
Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)
Rituximab (375 mg/m2) with FFP will be given every two weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892827

Locations
Israel
Wolfson MC Recruiting
Holon, Israel, 58100
Contact: Abraham Klepfish, MD    972-35028778    klepfish@wolfson.health.gov.il   
Sub-Investigator: Goldstein Daniela, MD         
Sub-Investigator: Gil Lugassy, Prof.         
Sub-Investigator: Ami Schattner, Prof.         
Sponsors and Collaborators
Wolfson Medical Center
  More Information

No publications provided

Responsible Party: Dr. Klepfish A., Director of Blood Bank, Wolfson Medical Center, Holon, Israel
ClinicalTrials.gov Identifier: NCT00892827     History of Changes
Other Study ID Numbers: AK- 01
Study First Received: May 4, 2009
Last Updated: September 12, 2010
Health Authority: Israel: Ministry of Health

Keywords provided by Wolfson Medical Center:
Rituximab
Mabthera
FFP
Fresh Frozen Plasma
CLL
Complement
Response
Overall response rate of FFP+Rituximab combined therapy
Analysis of complement activation pathways prior to, during and
after the study treatment.
Time to disease progression
Time to re-treatment (See Appendix I).
Safety of the combination treatment of FFP and RTX.

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014