Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of California, Davis
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01716208
First received: October 25, 2012
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Ofatumumab + Fresh Frozen Plasma
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Ofatumumab and Fresh Frozen Plasma in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Response to therapy [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Defined as complete, or partial response, and progression-free survival. Measured by National Cancer Institute - Working Group and International Workshop on Chronic Lymphocytic Leukemia


Secondary Outcome Measures:
  • Toxicity [ Time Frame: Up to two years ] [ Designated as safety issue: Yes ]
    Toxicities will be graded according to the NCI CTCAE v4.0.

  • Overall Survival [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
    Overall survival wil be measured as the time from start of treatment to the Date of death or the last date the patient was known to be alive

  • Complement levels (CH50 and C2 levels) [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
    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. Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of complement system.


Estimated Enrollment: 36
Study Start Date: January 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: Ofatumumab + Fresh Frozen Plasma
Other Name: Azerra

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716208

Contacts
Contact: Corinne Turrell 916-734-3089

Locations
United States, California
University of California Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Clinical Trials Navigator    916-734-3089      
Sponsors and Collaborators
University of California, Davis
GlaxoSmithKline
Investigators
Principal Investigator: Joseph Tuscano, MD University of California, Davis
  More Information

No publications provided

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01716208     History of Changes
Other Study ID Numbers: UCDCC#232, OFT116066
Study First Received: October 25, 2012
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, Davis:
Fresh Frozen Plasma
Complement
Monoclonal Antibody

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell

ClinicalTrials.gov processed this record on September 30, 2014