Clinical trial NCT01716208: Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma
Official title: Phase II Trial of Ofatumumab and Fresh Frozen Plasma in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Fresh Frozen Plasma
Complement
Monoclonal Antibody
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2012-10-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response to Therapy
timeFrame: Up to 37 months.
Secondary outcomes:
measure: Number of Participants With Toxicities
timeFrame: Up to two years
measure: Overall Survival
timeFrame: Up to two years
measure: Percent Reduction in Complement Levels (CH50)
timeFrame: Up to two weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Joseph Tuscano, MD
role: PRINCIPAL_INVESTIGATOR
References: