Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma

NCT ID: NCT01716208

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-14
• Study Completion Date: 2020-10-01

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ofatumumab + Fresh Frozen Plasma

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).

Group Type: EXPERIMENTAL

Ofatumumab + Fresh Frozen Plasma

Intervention Type: DRUG

Interventions

Ofatumumab + Fresh Frozen Plasma

Intervention Type: DRUG

Other Intervention Names

Azerra

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Joseph Tuscano

OTHER

Sponsor Role: lead

Responsible Party

Joseph Tuscano

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Joseph Tuscano, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California Comprehensive Cancer Center

Sacramento, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UCDCC#232

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OFT116066

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

333961

Identifier Type: -

Identifier Source: org_study_id