| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Monoclonal B-Cell Lymphocytosis |
| Purpose: |
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Background:
- Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell
lymphoma (MCL) are types of cancers in which there are too many abnormal lymphocytes (a
type of white blood cell). Monoclonal B-cell lymphocytosis (MBL) is a condition in
which the individual has a larger than normal number of lymphocytes. Individuals with
CLL, SLL, MBL, and MCL may survive for many years without the need for treatment, but
there is an apparent correlation between cell birth rates and disease activity. By
studying the birth and death rates of lymphocytes, researchers hope to identify
individuals who are at risk for worsening disease.
- Heavy water is similar in structure to regular water, but it has two deuterium atoms
instead of two hydrogen atoms. Deuterium has one more neutron than hydrogen, which is
what makes heavy water heavy. Heavy water is not radioactive, looks and tastes like
regular water, and has no known harmful effects at research-level doses. When a small
amount of heavy water is consumed daily, newly produced blood cells are labeled
(tagged), which allows researchers to track cell growth and to measure the birth and
death rates of CLL, SLL, MBL, MCL or normal lymphocytes.
Objectives:
- To study the birth and death rates of lymphocytes from individuals with MBL, CLL/SLL, and
MCL, compared with lymphocytes from healthy volunteers.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with MBL, CLL, SLL, or
MCL, but who have not been taking certain agents (Viagra, Levitra, Cialis, or other
PDE-inhibitors, prednisone, cyclosporin-A, rapamycin, or other immunosuppressive
agents, more than 2 cups of green tea daily, or Celebrex) for 4 weeks prior to
enrollment in the study.
- Healthy volunteers at least 18 years of age, but who have not been taking certain
agents (Viagra, Levitra, Cialis, or other PDE-inhibitors, prednisone, cyclosporin-A,
rapamycin, or other immunosuppressive agents, more than 2 cups of green tea daily, or
Celebrex)for 4 weeks prior to enrollment in the study.
Design:
- Participants will be screened with a medical history, physical examination, and initial
blood tests. Other tests may be administered to the individuals with cancer, as
required by the study researchers.
- All participants will drink regular doses of heavy water daily for a total of 4 weeks
(labeling period). There is an optional 6-month follow-up or wash-out period during
which no additional heavy water will be consumed.
- Blood samples will be collected weekly during the labeling period, and a bone marrow
biopsy will be obtained where possible. Individuals with cancer may also have a lymph
node biopsy during this part of the study.
- Additional blood samples may be collected during the optional wash-out phase of the
study to determine the rate at which cancer cells disappear.
- Treatment is not provided as part of this protocol.
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| Study summary: |
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Chronic lymphocytic leukemia (CLL) and its lymphoma variant, small lymphocytic lymphoma
(SLL) were for decades considered diseases caused by the progressive accumulation of
abnormal lymphocytes. The prevailing view being that CLL and SLL disease processes were
driven by an underlying defect in apoptosis. While resistance to apoptosis appears to be
important in the CLL and SLL disease process, recent studies suggest that cellular
proliferation is more important than previously realized.
Cells from individuals with CLL who drank deuterated water (heavy water) for 6 weeks showed
a turnover rate of 0.1 % to 1.1 % per day. In a second study involving CLL subjects who
drank heavy water, average CLL turnover rates were in a similar range but approximately
2-fold lower than average B-cell turnover rates from healthy individuals. These studies have
shown the safety and scientific value of using heavy water to study the kinetics of cell
proliferation in patients and normal volunteers.
We now propose this study to expand on findings by other investigators. This study will
address the site of proliferation for CLL/SLL cells and will include individuals with
monoclonal B-cell lymphocytosis (MBL), a possible precursor of CLL. Furthermore, we will
include patients with mantle cell lymphoma (MCL), a disease in which tumor proliferation
plays an important role.
Study participants will drink heavy water daily for a total of 4 weeks (labeling period)
with an optional 6 months follow up ( wash out period). Blood samples will be obtained
weekly during the labeling period. A bone marrow and/or lymph node biopsy will be obtained
where possible during the labeling period. Additional blood draws may be obtained during the
optional wash-out phase of the study to determine the rate at which tumor cells disappear.
The primary objective of this exploratory study is to obtain an estimate of the
proliferation rate of tumor cells in individuals with MBL, CLL/SLL, and MCL. Secondary
objectives include the comparison of proliferation rates between different anatomic
compartments, specifically peripheral blood, lymph node, and bone marrow and the estimation
of the attrition or disappearance rate of cells during an optional phase of the protocol.
Healthy volunteers may be included for comparison.
The primary endpoint is the estimate of the cell proliferation rate of tumor cells in
individuals with MBL, CLL/SLL, and MCL.
Secondary endpoints include: Proliferation rate in tissue compared to blood, disappearance
rate of labeled cells from the blood and tissue, and the safety profile of heavy water in
the study population. |
| Criteria: |
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- INCLUSION CRITERIA: (MBL, CLL/SLL, MCL group)
4.1.1. Diagnosed with CLL/SLL, MCL, or MBL
4.1.2. Greater than or equal to 18 years of age
4.1.3. Neutrophil count (ANC) greater than or equal to 1000/mcL
4.1.4. Platelet count greater than or equal to 50K/mcL
EXCLUSION CRITERIA: (MBL, CLL/SLL, MCL group)
4.2.1. Concomitant use of agents that have been described to affect the biology and/or
proliferation rate of CLL cells but are not approved or accepted therapies for CLL, SLL,
MCL, or MBL
- PDE-inhibitors (e.g. sildenafil, theophylline)
- Immunosuppressive agents (e.g., prednisone, cyclosporin-A, rapamycin)
- Green Tea extract (more than 2 cups per day)
- Cox-2 inhibitors
4.2.2. Chronic or current clinically significant infection, including HIV or uncontrolled
infection
4.2.3. Receiving concurrent anticancer therapies
4.2.4. Women who are pregnant or nursing, as well as women of childbearing potential who
are unwilling to use a an agreed upon form of contraception for the duration of
participation in this study
4.2.5 Sexually active males who are unwilling to follow the strict contraception
requirements described in this protocol.
4.2.6 Inability to understand the investigational nature of the study, inability to
provide informed consent
INCLUSION CRITERIA: (Healthy volunteer group)
4.3.1 Health status will be confirmed by brief History and Physical Exam and blood work
4.3.2 Greater than or equal to 18 years of age
4.3.3 CBC and coagulation panel within the expected normal ranges for the subject
EXCLUSION CRITERIA: (Healthy volunteer group)
4.4.1. Concomitant use of agents that have been described to affect the biology and/or
proliferation rate of CLL cells
- PDE-inhibitors (e.g. , slidenafil, theophylline)
- Immunosuppressive agents (e.g., cyclosporin-A, rapamycin)
- Green Tea extract (more than 2 cups per day)
- Cox-2 inhibitors
4.4.2. Women who are pregnant or nursing, as well as women of childbearing potential who
are unwilling to use an agreed upon form of contraception for the duration of study
participation.
4.4.3 Sexually active males who are unwilling to follow the strict contraception
requirements described in this protocol.
4.4.4. Inability to understand the investigational nature of the study, inability to
provide informed consent |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 23, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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