A Study of the Kinetics of Lymphoid Cells in Patients With Monoclonal B-cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL) and Healthy Volunteers
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies, Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology, Other |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 12/26/2018 |
| Start Date: | June 3, 2010 |
| Contact: | Clare C Sun, M.D. |
| Email: | clare.sun@nih.gov |
| Phone: | (301) 451-7130 |
A Study of the Kinetics of Lymphoid Cells in Patients With Monoclonal B-Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL) and Healthy Volunteers.
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.
- 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.
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.
The secondary objectives are to compare 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.
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.
The secondary objectives are to compare 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.
- INCLUSION CRITERIA: (MBL, CLL/SLL, MCL group)
4.1.1.
4.1.2.
4.1.3.
4.1.4.
EXCLUSION CRITERIA: (MBL, CLL/SLL, MCL group)
4.2.1.
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.
uncontrolled infection
4.2.3.
4.2.4.
who are unwilling to use a an agreed upon form of contraception for the duration of
participation in this study
4.2.5
requirements described in this protocol.
4.2.6
provide informed consent
INCLUSION CRITERIA: (Healthy volunteer group)
4.3.1
4.3.2
4.3.3
EXCLUSION CRITERIA: (Healthy volunteer group)
4.4.1.
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.
who are unwilling to use an agreed upon form of contraception for the duration of study
participation.
4.4.3
requirements described in this protocol.
4.4.4.
provide informed consent
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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