Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Hyperplasia

Lymphocytosis

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Lymphoma, Non-Hodgkin

Leukocytosis

Leukocyte Disorders

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Clare C Sun, M.D.

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) 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 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 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.

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

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.

Northwell Health

National Heart, Lung, and Blood Institute (NHLBI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Prostatic Neoplasms

Inflammation

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Quality of Life

Other Dietary Supplements

All Drugs and Chemicals

Herbal and Botanical

Omega 3 Fatty Acid

Sunflower

3g per day of purified EPA, capsules, to be taken once a day, for 14 months.

3 g per day of high-oleic sunflower oil capsules, to be taken once a day, for 14 months.

3g/day of purified EPA , capsules, taken once daily, for 14 months

3g/day of placebo (high oleic sunflower oil) , capsules, taken once daily, for 14 months

Placebo

Vincent Fradet, MD, PhD

Prostate cancer, the most frequently diagnosed cancer among occidental men, is associated with a major individual and societal burden. Although still controversial, the literature suggests that a high consumption of omega-3 fatty acids (ω3) has protective effects against prostate cancer. One of the proposed mechanisms of action of ω3 lies in their anti-inflammatory properties. In addition, there are some observational evidences suggesting an association of ω3 intake with a lower rate of depression in cancer patients. However, no clinical study has tested the efficacy of ω3 supplementation on psychological and quality of life outcomes in that population. Several evidences point to a possible involvement of inflammation in psychological issues. Reducing the systemic inflammatory state may have beneficial impact on the quality of life of these patients. Preliminary work from this team of investigators, in a cohort of patients managed with active surveillance for their low-grade prostate cancer, show a strong inverse association between the risk of prostate cancer progression (to high-grade) and the level of prostatic eicosapentanoic acid (EPA- a type of ω3).

HYPOTHESIS: EPA-rich monoglycerides fish oil (MAG-EPA) has global positive effects on prostate cancer cell proliferation, inflammation and on the patient's psychosocial functioning and quality of life.

The investigators propose a double blind, randomized controlled clinical trial. 130 consecutive patients suffering from high-risk prostate cancer who choose to be treated by radical prostatectomy will be eligible to this study. The presence of high-grade cancer will be mandatory.

The intervention, a daily supplementation with 3g supplement of fish oil monoglycerides rich in EPA, vs. placebo capsules containing high oleic sunflower oil, will start six weeks before the prostatectomy and will continue for one year after surgery. The potential confounding variables will be measured before the start of the intervention: age, anthropometric parameters, stage and clinical and pathological tumor grade (Gleason score), pre-operative level of prostate specific antigen and diet.

This project proposes a simple intervention by dietary supplementation that could eventually help to reduce the incidence and/or progression of prostate cancer, and the consequences of its treatment, and thus could contribute to diminish the heavy individual and societal burden of prostate cancer. The clinical data generated by this trial will serve as solid basis for a large-scale phase III clinical trial.

Effects of EPA on Prostate Cancer Cells Proliferation and Quality of Life

Étude randomisée, contrôlée, de Phase II, Effets d'un Supplement d'oméga-3 (EPA) Sur l'Inflammation, la prolifération Cellulaire et la qualité de Vie Chez Des Patients Avec Cancer de la Prostate traités Par Prostatectomie Radicale

The difference of fatty acid levels between both groups, relative to baseline, will be quantified using gas chromatography coupled with mass spectrometry and expressed as relative percentages of total fatty acids.

The difference of fatty acid levels between both groups at prostatectomy will be quantified using gas chromatography coupled with mass spectrometry and expressed as relative percentages of total fatty acids, and in absolute level (mg per gram of tissue).

The difference in perioperative bleeding, laboratory tests (hemoglobin, hematocrit and platelets) and surgical complications between both group will be examined at surgery.

Pathological reclassification of cancer grade (ISUP grading system) and stage between the prostate diagnostic biopsy and the prostatectomy specimen will be compared between both groups.

PSA change relative to baseline will be measured for both groups.

The biochemical recurrence, defined as a PSA level ≥ 0.2 ng/mL after reaching a non-detectable level at three months post-surgery, will be evaluated for both groups.

At 6 weeks post study entry, the prostate of the patient will be removed by prostatectomy. The tissue will be preserved in paraffin blocks. The tumour will be identified and the level of Ki-67 in the tumour will be quantified.

The changes in levels of systemic inflammatory mediators, relative to their baseline levels, at the time of radical prostatectomy and at one year post-radical prostatectomy, will be measured. The levels of mediators will be expressed in pg/mL and quantified using validated techniques.

The differences in the levels of expression of inflammatory mediators between both treatment groups will be measured in the peripheral zone of the prostate before surgical prostate dissection/ischemia. The levels of mediators will be expressed in pg/mL and quantified using validated techniques. Further validation could be performed using immunohistochemistry techniques.

Validated questionnaires will be used to measure the modulation of the treatment on Quality of Life of the patients, which will include questions on mood, anxiety levels, sleep and cognition.

Validated questionnaires will be used to measure the modulation of the treatment on psychosocial functioning of the patients, which will include questions on mood, anxiety levels, sleep and cognition.

The impact of changes in inflammatory mediators levels induced by EPA supplementation on quality of life scores will be measured. To do so, we will use appropriate and powerful statistical tests.

The impact of changes in inflammatory mediators levels induced by EPA supplementation and changes in psychosocial functioning scores will be measured. To do so, we will use appropriate and powerful statistical tests.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT01117142	Lymphoma, Mantl... CLL (Chronic Ly... Monoclonal B-Ce... Healthy Volunte... Small Lymphocyt...		18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Effects of EPA on Prostate Cancer Cells Proliferation and Quality of Life	NCT02333435	Prostate Cancer	EPA Placebo	18 Years -	CHU de Quebec-Universite Laval

Spots Global Cancer Trial Database for cellular proliferation