Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Ofatumumab + Fresh Frozen Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a pathological diagnosis of B-cell CLL. Patients must have received prior rituximab therapy and must have recovered from all non-hematologic toxicities. (Previous radiation is allowed as long as patients have recovered from all treatment related toxicities). Patients must meet the following laboratory values: Hgb > 9.0 g/dl Platelets > 50,000/mm3 Creatinine < 2.0 times the institutional upper limit of normal SGOT/SGPT < 2.5 times the institutional upper limit of normal Total Bilirubin <1. 5 times the institutional upper limit of normal Alkaline phosphatase <2.5 times upper limit of normal (unless due to disease involvement of the liver or bone marrow) Patients must be at least 18 years of age. Patients must have a performance status of 0-2 by ECOG criteria. All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional and federal guidelines. Exclusion Criteria: Subjects who have current active hepatic or biliary disease. Having received rituximab or rituximab-containing therapy within the prior 3 months. Treatment with any known therapeutic or experimental therapy within 4 weeks prior to enrollment, or currently participating in any other interventional clinical study. Other past or current malignancy. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae. Known HIV positive. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result. Pregnant or lactating women. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy. Receiving warfarin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ofatumumab + Fresh Frozen Plasma<br>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). | Drug: Ofatumumab + Fresh Frozen Plasma<br> <br> * Other names: Azerra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Therapy | Defined as complete, or partial response, and progression-free survival. Measured by National Cancer Institute - Working Group and International Workshop on Chronic Lymphocytic Leukemia | Up to 37 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Toxicities | Toxicities will be graded according to the NCI CTCAE v4.0. | Up to two years | 
| Overall Survival | Count of participants known to be alive up to two years from the time from start of treatment. | Up to two years | 
| Percent Reduction in Complement Levels (CH50) | 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. | Up to two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fresh Frozen Plasma, Complement, Monoclonal Antibody