Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Complement System Proteins

Ofatumumab

Ofatumumab will be infused intravenously on day 1 (300 mg initial dose), followed one week later by 2000 mg weekly for 7 doses, followed 4 weeks later by 2000 mg every 4 weeks for 4 doses. Two units (approximately 200 or 250 ml) of FFP will be administered prior to ofatumumab(with the exception of the first dose). A unit of fresh frozen plasma is approximately 250ml (or half a pint).

Ofatumumab + Fresh Frozen Plasma

Joseph Tuscano, MD

It has been shown that many patients with lymphoma or chronic lymphocytic leukemia (CLL)have low levels of complement. Several drugs have been approved by the Food and Drug Administration (FDA) for use in this cancer. However, these drugs are often used as combination therapies which means two or more drugs are part of the treatment. Many people, especially elderly patients, cannot put up with the use of multiple drugs because of the side effects.

The main purpose of this study is to see if patients respond to therapy with human plasma (known as fresh frozen plasma or FFP) and ofatumumab. Another purpose of the study is to find out if this therapy will increase chances of getting rid of leukemia. This study will also look at the levels of complement in your blood. The levels of complement may allow better understanding of whether increasing the levels of complement by giving FFP may help control leukemia.

The vast majority of patients with CLL are elderly and often they cannot tolerate standard multi-agent chemotherapeutic or biochemotherapeutic approaches. Based on this, less toxic and more effective treatment options are needed.

Ofatumumab has proven to be effective in patients with relapsed and/or refractory CLL. Previous studies have shown that ofatumumab is more effective than rituximab at activating complement and utilizing complement-dependent cytotoxicity (CDC).

This study will investigate treating relapsed/refractory CLL patients with FFP in combination with ofatumumab. The hypothesis is that patients with CLL have low complement levels and when they get treated with humanized antibodies like rituximab or ofatumumab these levels drop even further. Both these antibodies utilize complement to exert their cytotoxic effect, thus we hypothesize that by replacing complement levels with FFP we can enhance the efficacy of ofatumumab.

Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma

Phase II Trial of Ofatumumab and Fresh Frozen Plasma in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Defined as complete, or partial response, and progression-free survival. Measured by National Cancer Institute - Working Group and International Workshop on Chronic Lymphocytic Leukemia

Toxicities will be graded according to the NCI CTCAE v4.0.

Count of participants known to be alive up to two years from the time from start of treatment.

Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity.

GlaxoSmithKline

Joseph Tuscano

Principal Investigator

Incidence of adverse events according to the Common Terminology Criteria for Adverse Events Version 4.0

Ofatumumab will be infused intravenously on day 1 (300 mg initial dose), followed one week later by 2000 mg weekly for 7 doses, followed 4 weeks later by 2000 mg every 4 weeks for 4 doses. Two units (approximately 200 or 250 ml) of FFP will be administered prior to ofatumumab(with the exception of the first dose). A unit of fresh frozen plasma is approximately 250ml (or half a pint).

Ofatumumab + Fresh Frozen Plasma

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Analyst

Response to Therapy

Blood bilirubin increased

Chills

Constipation

Cough

Creatinine increased

Dehydration

Dizziness

Dyspepsia

Dyspnea

Blepharitis

Fatigue

Flushing

Gastroesophageal reflux disease

Feverish

Generalized muscle weakness

Headache

Hiccups

Hyperkalemia

Hypertension

Hypocalcemia

hyponatremia

Infusion related reaction

Insomnia

Lung infection

Lymph node pain

Lymphocyte count increased

Nausea

Neutrophil count decreased

Palpitations

Paresthesia

peripheral sensory neuropathy

Platelet count decreased

Rash acneiform

Rash maculo-papular

Aspergillus Pneumonia

Sinus tachycardia

Sinusitis

Rash

Lesions on face, neck, scalp

Guttate Psoriasis (Exacerbation of Symptoms)

Skin infection, Eyelid

Upper respiratory infection

Wheezing

White blood cell decreased

Number of Participants With Toxicities

Overall Survival

Percent Reduction in Complement Levels (CH50)

Overall Study

Disease Progression

Antirheumatic Agents

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

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

Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)

Abraham Klepfish, MD

Goldstein Daniela, MD

Gil Lugassy, Prof.

Ami Schattner, Prof.

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.

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.

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

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.

Wolfson Medical Center

Dr. Klepfish A., Director of Blood Bank

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma	NCT01716208	Chronic Lymphoc...	Ofatumumab + Fr...	18 Years -	University of California, Davis
Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia	NCT00892827	Advanced Refrac...	Rituximab (Mabt...	18 Years -	Wolfson Medical Center

Spots Global Cancer Trial Database for complement

Every month we try and update this database with for complement cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for complement

Every month we try and update this database with for complement cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for complement cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.