Chronic Lymphocytic LeukemiaPhase 2NCT01716208
Ofatumumab and Fresh Frozen Plasma in Patients With Chronic Lymphocytic Lymphoma
A Phase 2 study testing Ofatumumab + Fresh Frozen Plasma in people with Chronic Lymphocytic Leukemia, run by Joseph Tuscano at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Ofatumumab + Fresh Frozen Plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2013to 1 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase II Trial of Ofatumumab and Fresh Frozen Plasma in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
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.
Read the 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
- Being tested
- Ofatumumab + Fresh Frozen Plasma
- Keywords
- Fresh Frozen Plasma, Complement, Monoclonal Antibody
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ofatumumab + Fresh Frozen PlasmaDrug
Also called Azerra
| Study group | Role | What they receive |
|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Experimental | 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). Receives: Drug: Ofatumumab + Fresh Frozen Plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 37 months.
Secondary outcomes (3)
Number of Participants With Toxicities
Toxicities will be graded according to the NCI CTCAE v4.0.
Measured: Up to two years
Overall Survival
Count of participants known to be alive up to two years from the time from start of treatment.
Measured: 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.
Measured: Up to two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study start14 Jan 2013
- Primary completion1 Oct 2019
- Study completion1 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Tuscano
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor-investigator, Joseph Tuscano, University of California, Davis
- Investigators
- Joseph Tuscano, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01716208
- Sponsor's protocol ID
- 333961
- Other IDs
- UCDCC#232, OFT116066
- Status last verified
- Apr 2021
- First submitted
- 25 Oct 2012
- Last updated
- 11 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Ofatumumab and Fresh Frozen Plasma in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01716208
- Acronym / sponsor ID
- 333961
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Fresh Frozen Plasma, Complement, Monoclonal Antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Joseph TuscanoUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 14 Jan 2013 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 29 Oct 2012 (estimated)
- Results
- Posted 11 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Experimental | Drug: Ofatumumab + Fresh Frozen PlasmaOfatumumab 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- Patients must be at least 18 years of age.
- Patients must have a performance status of 0-2 by ECOG criteria.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ofatumumab + Fresh Frozen PlasmaAlso: Azerra | Drug | Ofatumumab + Fresh Frozen Plasma |
Primary outcome
Response to Therapy
Time frame: Up to 37 months.
Defined as complete, or partial response, and progression-free survival. Measured by National Cancer Institute - Working Group and International Workshop on Chronic Lymphocytic Leukemia
3 secondary outcomes
Number of Participants With Toxicities
Time frame: Up to two years
Overall Survival
Time frame: Up to two years
Percent Reduction in Complement Levels (CH50)
Time frame: Up to two weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Tuscano, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ofatumumab + Fresh Frozen Plasma in people with Chronic Lymphocytic Leukemia, run by Joseph Tuscano at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to Therapy (time frame: Up to 37 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021; AzTrials last refreshed its copy on 8 Nov 2026.