Chronic Lymphocytic Leukemia, Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma
Conditions
Keywords
ES-CLL, MGUS, SMM, Early Stage - Chronic Lymphocytic Leukemia
Brief summary
Escalating doses of Omega 3 Fatty Acids are being used in patients who have early stage Chronic Lymphocytic Leukemia (ES-CLL), Monoclonal Gammopathy of Undetermined Significance (MGUS), or Smoldering Multiple Myeloma (SMM), whose disease does not currently require treatment. The primary aim of the study is to determine if the Omega 3 supplementation will help prevent or delay progression of the disease to a stage that requires treatment.
Interventions
DIETARY_SUPPLEMENTOmega 3 Fatty Acid
Omega 3 supplementation will be initiated at three 1250 mg capsules daily for the first month. If dose is well tolerated, it will be increased to six 1250 mg capsules daily for 30 days, and finally to nine 1250 mg capsules daily. Treatment period is 12 months.
Sponsors
Edwards Foundation, Inc.
Marshall University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be over 18 years of age. * Must be free of other medical conditions that would decrease life expectancy to less that 12 months. * Must be free of Omega 3 supplements or other fish oil containing nutritional supplements for a minimum of two months prior to enrollment. * Must have a ECOG performance status of 0,1 or 2.
Exclusion criteria
* Any life-threatening condition such as (but not limited to) advanced heart disease, kidney or liver failure with an expected survival of less than 12 months. * Any other active malignancy. * Women who are pregnant or lactating. * Individuals unable to give informed consent. * Individuals with known allergy or intolerance to fish oil supplements. * Any patient with an active bleeding diatheses or disorder. * ECOG performance status of 3 or 4.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | baseline, and post supplement month 1(3 capsules/day), month 2 (6capsules/day), month 3 (9 capusules/day), month 6 (9 capusules/day), month 9 (9 capusules/day), month 12 (post supplement) | Peripheral lymphocytes were isolated from the blood using Ficoll-Paque gradient. Nuclear Factor Kappa B activation was analyzed using Thermo Scientific Transcription Factor kit for NFkB p50, according to manufacturer's protocol. Protein extracts containing 1-15µg of protein/well were added in triplicates. Luminescence resulting from a reaction with bound NFkB was detected using a Berthold Centro LB960 Luminometer and analyzed with MikroWin 2000 ver. 1.08. NFkB activity was normalized by luminescence units/µg of protein per well. |
| The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | Baseline, month 1, month 2, month 3, month 6, month 9, 12 months | Patients diagnosed with early stage (asymptomatic) CLL were supplemented with escalating doses of omega-3 (n-3) fatty acids (2.4 g of n-3/day up to 7.2 g of n-3/day). Given that these patients are asymptomatic and did not require treatment, measures of tumor mass during and after omega-3 supplementation, as evaluated by standard clinical tests of disease activity, were not performed. Instead, absolute lymphocyte counts (ALC), as a measure of tumor burden, was evaluated before and after omega-3 supplementation. Data represents the fold change in ALC post omega-3 consumption as compared to baseline ALC. Patients with MGUS or SMM were not enrolled into this study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omega 3 Supplementation | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Omega 3 Supplementation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age Continuous | 68 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement.
Peripheral lymphocytes were isolated from the blood using Ficoll-Paque gradient. Nuclear Factor Kappa B activation was analyzed using Thermo Scientific Transcription Factor kit for NFkB p50, according to manufacturer's protocol. Protein extracts containing 1-15µg of protein/well were added in triplicates. Luminescence resulting from a reaction with bound NFkB was detected using a Berthold Centro LB960 Luminometer and analyzed with MikroWin 2000 ver. 1.08. NFkB activity was normalized by luminescence units/µg of protein per well.
Time frame: baseline, and post supplement month 1(3 capsules/day), month 2 (6capsules/day), month 3 (9 capusules/day), month 6 (9 capusules/day), month 9 (9 capusules/day), month 12 (post supplement)
Population: NFkB activation of all patients diagnosed with early stage CLL at baseline and following omega 3 consumption. Patients are further separated into high (\> median, n=7) and low initial baseline (\< median, n=6) NFkB. Patients included must have had one baseline and at least one period of omega 3 consumption. Not all patients completed all periods
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baseline Nuclear Factor Kappa B Activation | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Total Population | 7.2 10^6 NFkB Luminescence units/µg protein | Standard Error 2.25 |
| Baseline Nuclear Factor Kappa B Activation | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Lower Initial Expressers | 0.8 10^6 NFkB Luminescence units/µg protein | Standard Error 0.27 |
| Baseline Nuclear Factor Kappa B Activation | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Higher Initial Expressers | 12.8 10^6 NFkB Luminescence units/µg protein | Standard Error 2.77 |
| Nuclear Factor Kappa B Activation Following 3 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Higher Initial Expressers | 7.4 10^6 NFkB Luminescence units/µg protein | Standard Error 2.41 |
| Nuclear Factor Kappa B Activation Following 3 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Total Population | 4.1 10^6 NFkB Luminescence units/µg protein | Standard Error 1.53 |
| Nuclear Factor Kappa B Activation Following 3 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Lower Initial Expressers | 0.9 10^6 NFkB Luminescence units/µg protein | Standard Error 0.37 |
| Nuclear Factor Kappa B Activation Following 6 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Higher Initial Expressers | 6.4 10^6 NFkB Luminescence units/µg protein | Standard Error 1.42 |
| Nuclear Factor Kappa B Activation Following 6 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Total Population | 4.2 10^6 NFkB Luminescence units/µg protein | Standard Error 1.15 |
| Nuclear Factor Kappa B Activation Following 6 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Lower Initial Expressers | 1.5 10^6 NFkB Luminescence units/µg protein | Standard Error 0.8 |
| Nuclear Factor Kappa B Activation Following 9 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Total Population | 0.7 10^6 NFkB Luminescence units/µg protein | Standard Error 0.94 |
| Nuclear Factor Kappa B Activation Following 9 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Lower Initial Expressers | 0.6 10^6 NFkB Luminescence units/µg protein | Standard Error 0.11 |
| Nuclear Factor Kappa B Activation Following 9 Capsules Per Day | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Higher Initial Expressers | 0.8 10^6 NFkB Luminescence units/µg protein | Standard Error 0.2 |
| Nuclear Factor Kappa B Activation Post Supplement | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Higher Initial Expressers | 1.6 10^6 NFkB Luminescence units/µg protein | Standard Error 1.44 |
| Nuclear Factor Kappa B Activation Post Supplement | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Total Population | 1.5 10^6 NFkB Luminescence units/µg protein | Standard Error 0.86 |
| Nuclear Factor Kappa B Activation Post Supplement | Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. | Lower Initial Expressers | 1.3 10^6 NFkB Luminescence units/µg protein | Standard Error 1.16 |
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on global response.p-value: 0.7895% CI: [-5, 11.2]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on global response.p-value: 0.7595% CI: [-4.6, 10.7]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on global response.p-value: 0.0895% CI: [-0.6, 13.7]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on global response.p-value: 0.1795% CI: [-1.6, 13.2]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on High Initial NFkB Activation Expressers.p-value: 0.6195% CI: [-6.5, 17.2]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on High Initial NFkB Activation Expressers.p-value: 0.3295% CI: [-4.1, 16.8]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on High Initial NFkB Activation Expressers.p-value: 0.0395% CI: [1.6, 22.3]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on High Initial NFkB Activation Expressers.p-value: 0.0495% CI: [0.5, 21.8]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on Low Initial NFkB Activation Expressers.p-value: 195% CI: [-1.5, 1.2]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on Low Initial NFkB Activation Expressers.p-value: 0.8895% CI: [-3.5, 2.3]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on Low Initial NFkB Activation Expressers.p-value: 0.9895% CI: [-0.8, 1]ANOVA
Comparison: Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.~Analysis based on Low Initial NFkB Activation Expressers.p-value: 0.9895% CI: [-6.6, 5.3]ANOVA
Primary
The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity.
Patients diagnosed with early stage (asymptomatic) CLL were supplemented with escalating doses of omega-3 (n-3) fatty acids (2.4 g of n-3/day up to 7.2 g of n-3/day). Given that these patients are asymptomatic and did not require treatment, measures of tumor mass during and after omega-3 supplementation, as evaluated by standard clinical tests of disease activity, were not performed. Instead, absolute lymphocyte counts (ALC), as a measure of tumor burden, was evaluated before and after omega-3 supplementation. Data represents the fold change in ALC post omega-3 consumption as compared to baseline ALC. Patients with MGUS or SMM were not enrolled into this study.
Time frame: Baseline, month 1, month 2, month 3, month 6, month 9, 12 months
Population: Patients who's absolute lymphocyte counts were known prior to omega-3 initiation (baseline) and after omega-3 consumption were included in this analysis. Patients who's ALC was unknown prior to omega-3 initiation or after omega-3 consumption were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Baseline Nuclear Factor Kappa B Activation | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.62 Fold Change |
| Nuclear Factor Kappa B Activation Following 3 Capsules Per Day | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.71 Fold Change |
| Nuclear Factor Kappa B Activation Following 6 Capsules Per Day | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 0.78 Fold Change |
| Nuclear Factor Kappa B Activation Following 9 Capsules Per Day | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 0.96 Fold Change |
| Nuclear Factor Kappa B Activation Post Supplement | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.32 Fold Change |
| Fold Change in ALC-Patient 6 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.08 Fold Change |
| Fold Change in ALC-Patient 7 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.00 Fold Change |
| Fold Change in ALC-Patient 8 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 0.92 Fold Change |
| Fold Change in ALC-Patient 9 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.49 Fold Change |
| Fold Change in ALC-Patient 10 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.05 Fold Change |
| Fold Change in ALC-Patient 11 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.16 Fold Change |
| Fold Change in ALC-Patient 13 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.03 Fold Change |
| Fold Change in ALC-Patient 14 | The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. | 1.22 Fold Change |