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
|First Received Date ICMJE||May 4, 2010|
|Last Updated Date||October 23, 2015|
|Start Date ICMJE||April 2010|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||To estimate the cell proilferation rate of tumor cells in individuals with MBL, CLL/SLL, and MCL.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01117142 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||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/|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||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|
|Official Title ICMJE||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.|
- To study the birth and death rates of lymphocytes from individuals with MBL, CLL/SLL, and MCL, compared with lymphocytes from healthy volunteers.
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.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Monoclonal B-Cell Lymphocytosis|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||105|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
4.1.1.< TAB> Diagnosed with MBL, CLL/SLL, or MCL
4.1.2.< TAB> Greater than or equal to 18 years of age
4.1.3.< TAB> Neutrophil count (ANC) greater than or equal to 1000/mcL
4.1.4.< TAB> Platelet count greater than or equal to 50K/mcL
EXCLUSION CRITERIA: (MBL, CLL/SLL, MCL group)
4.2.1.< TAB> 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
4.2.2.< TAB> Chronic or current clinically significant infection, including HIV or uncontrolled infection
4.2.3.< TAB> Receiving concurrent anticancer therapies
4.2.4.< TAB> 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< TAB> Sexually active males who are unwilling to follow the strict contraception requirements described in this protocol.
4.2.6< TAB> Inability to understand the investigational nature of the study, inability to provide informed consent
INCLUSION CRITERIA: (Healthy volunteer group)
4.3.1< TAB> Health status will be confirmed by brief History and Physical Exam and blood work
4.3.2< TAB> Greater than or equal to 18 years of age
4.3.3< TAB> CBC and coagulation panel within the expected normal ranges for the subject
EXCLUSION CRITERIA: (Healthy volunteer group)
4.4.1.< TAB> Concomitant use of agents that have been described to affect the biology and/or proliferation rate of CLL cells
4.4.2.< TAB> 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< TAB> Sexually active males who are unwilling to follow the strict contraception requirements described in this protocol.
4.4.4.< TAB> Inability to understand the investigational nature of the study, inability to provide informed consent
|Ages||18 Years to 99 Years|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01117142|
|Other Study ID Numbers ICMJE||100097, 10-H-0097|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||North Shore Long Island Jewish Health System|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP