Chronic Lymphocytic Leukemia
Conditions
Keywords
Fresh Frozen Plasma, Complement, Monoclonal Antibody
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.
Interventions
DRUGOfatumumab + Fresh Frozen Plasma
Sponsors
GlaxoSmithKline
Joseph Tuscano
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Therapy | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Toxicities | Up to two years | Toxicities will be graded according to the NCI CTCAE v4.0. |
| Overall Survival | Up to two years | Count of participants known to be alive up to two years from the time from start of treatment. |
| Percent Reduction in Complement Levels (CH50) | Up to two weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Ofatumumab + Fresh Frozen Plasma | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Ofatumumab + Fresh Frozen Plasma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 12 |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
Primary
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
Time frame: Up to 37 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Response to Therapy | PR | 10 Participants |
| Ofatumumab + Fresh Frozen Plasma | Response to Therapy | CR | 2 Participants |
Secondary
Number of Participants With Toxicities
Toxicities will be graded according to the NCI CTCAE v4.0.
Time frame: Up to two years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Blood bilirubin increased | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Chills | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Constipation | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Cough | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Creatinine increased | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Dehydration | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Dizziness | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Dyspepsia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Dyspnea | 3 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Blepharitis | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Lesions on face, neck, scalp | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Guttate Psoriasis (Exacerbation of Symptoms) | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Skin infection, Eyelid | 4 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Upper respiratory infection | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Wheezing | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Fatigue | 5 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Flushing | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Gastroesophageal reflux disease | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Feverish | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Generalized muscle weakness | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Headache | 4 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Hiccups | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Hyperkalemia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Hypertension | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Hypocalcemia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | hyponatremia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Infusion related reaction | 7 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Insomnia | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Lung infection | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Lymph node pain | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Lymphocyte count increased | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Nausea | 5 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Neutrophil count decreased | 4 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Palpitations | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Paresthesia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | peripheral sensory neuropathy | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Platelet count decreased | 4 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Rash acneiform | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Rash maculo-papular | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Aspergillus Pneumonia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Sinus tachycardia | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Sinusitis | 2 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | Rash | 1 Participants |
| Ofatumumab + Fresh Frozen Plasma | Number of Participants With Toxicities | White blood cell decreased | 3 Participants |
Secondary
Overall Survival
Count of participants known to be alive up to two years from the time from start of treatment.
Time frame: Up to two years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Overall Survival | 11 Participants |
Secondary
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.
Time frame: Up to two weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ofatumumab + Fresh Frozen Plasma | Percent Reduction in Complement Levels (CH50) | 54 Percentage change |