NCT01117142

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jun 2010

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 4, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 5, 2010

Completed
29 days until next milestone

Study Start

First participant enrolled

June 3, 2010

Completed
10.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 10, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 10, 2020

Completed
Last Updated

July 14, 2020

Status Verified

July 1, 2020

Enrollment Period

10.1 years

First QC Date

May 4, 2010

Last Update Submit

July 13, 2020

Conditions

Keywords

CLL (Chronic Lymphocytic Leukemia)Monoclonal B Cell LymphocytosisSmall Lymphocytic LymphomaMantle Cell LymphomaCellular ProliferationChronic Lymphocytic LeukemiaCLLMonoclonal B-Cell LymphocytosisMBLSLLMCLHealthy VolunteerHV

Outcome Measures

Primary Outcomes (1)

  • The primary endpoint is the estimate of the cell proliferation rate of tumor cells in individuals with MBL, CLL/SLL, and MCL

    Cell proliferation rate of tumor cells

    28 days

Secondary Outcomes (1)

  • 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/

    28 to 196 days

Study Arms (4)

CLL/SLL

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Healthy Volunteers

Healthy Volunteers

MBL

Monoclonal B-cell lymphocytosis

MCL

Mantle Cell Lymphoma

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

All patients with eligible conditions or healthy volunteers aged 18 and over if participating as a normal volunteer who otherwise fulfill the eligibility criteria will be considered for the protocol.

You may qualify if:

  • \<TAB\>Diagnosed with MBL, CLL/SLL, or MCL
  • \<TAB\>Greater than or equal to 18 years of age
  • \<TAB\>Neutrophil count (ANC) greater than or equal to 1000/mcL
  • \<TAB\>Platelet count greater than or equal to 50K/mcL

You may not qualify if:

  • \<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
  • 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
  • \<TAB\>Chronic or current clinically significant infection, including HIV or uncontrolled infection
  • \<TAB\>Receiving concurrent anticancer therapies
  • \<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
  • \<TAB\>Sexually active males who are unwilling to follow the strict contraception requirements described in this protocol.
  • \<TAB\>Inability to understand the investigational nature of the study, inability to provide informed consent
  • \<TAB\>Health status will be confirmed by brief History and Physical Exam and blood work
  • \<TAB\>Greater than or equal to 18 years of age
  • \<TAB\>CBC and coagulation panel within the expected normal ranges for the subject
  • \<TAB\>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)
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998 Jan 1;91(1):3-21.

    PMID: 9414264BACKGROUND
  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

    PMID: 19474385BACKGROUND
  • Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL. A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL). Eur J Cancer Care (Engl). 2005 Mar;14(1):53-62. doi: 10.1111/j.1365-2354.2005.00513.x.

    PMID: 15698386BACKGROUND

Related Links

MeSH Terms

Conditions

Lymphoma, Mantle-CellLeukemia, B-CellLeukemia, Lymphocytic, Chronic, B-CellHyperplasia

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Clare C Sun, M.D.

    National Heart, Lung, and Blood Institute (NHLBI)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 4, 2010

First Posted

May 5, 2010

Study Start

June 3, 2010

Primary Completion

July 10, 2020

Study Completion

July 10, 2020

Last Updated

July 14, 2020

Record last verified: 2020-07

Locations