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Curcumin to Improve Inflammation and Symptoms in Patients With Clonal Cytopenia of Undetermined Significance, Low Risk Myelodysplastic Syndrome, and Myeloproliferative Neoplasms

Primary Purpose

Clonal Cytopenia of Undetermined Significance, Essential Thrombocythemia, Myelodysplastic Syndrome

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Biospecimen Collection
Bone Marrow Aspiration
Bone Marrow Biopsy
Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement
Piperine Extract (Standardized)
Placebo Administration
Questionnaire Administration
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clonal Cytopenia of Undetermined Significance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >= 18 Eastern Cooperative Oncology Group (ECOG) =< 2 Ability to understand and willingness to sign a written informed consent Diagnosis of polycythemia vera (PV), essential thrombocytosis (ET) or myelofibrosis (MF) per World Health Organization (WHO) 2016 diagnostic criteria Presence of at least one symptom measurable using the MPN-/Symptom Assessment Form (SAF) with a severity greater than 3 MPN patients determined to have stable disease undergoing surveillance and unlikely to require initiation of new cytoreductive therapy (i.e., hydroxyurea, ruxotinib, interferon within the study period); patients on a stable dose of hydroxyurea for at least 6 months who meet the other inclusion/exclusion criteria may be included A diagnosis of CCUS or LR-MDS CCUS defined as persistent cytopenia for > 6 months (hemoglobin [Hgb] < 11.3 g/dL [7 mmol/L] in women and Hgb < 12.9 g/dL [8 mmol/L] in men, platelet < 150 x 10^9/L or neutrophils < 1.8 x 10^9/L), normal cytogenetics, presence of detectable MDS associated mutations and bone marrow morphology non-diagnostic of MDS or any other malignancies LR-MDS as defined by WHO 2016 diagnosis criteria Minimum baseline symptom score of 25 in the fatigue section of the symptom questionnaire Exclusion Criteria: Patients with intake of curcumin as a dietary supplement, including multivitamin and unwillingness to quit more than 24 hours before study start Patients with inability to understand and adhere to information given Patients receiving active treatment for another malignancy except with hormonal therapy for a malignancy considered to be in remission or growth factors (erythropoietin, granulocyte colony-stimulating factor [G-CSF] and luspatercept) Patients with intermediate or high-risk MDS Patients must not be pregnant or nursing Patients must not be on any oral or intravenous steroid or any other anti-inflammatories (ibuprofen > 200mg/week or 400mg/month, naproxen of any dose, > 325mg aspirin daily, any herbal anti-inflammatory concoction of any dose)

Sites / Locations

  • Los Angeles County-USC Medical Center
  • USC / Norris Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (C3 Complex/Bioperine)

Arm II (placebo)

Arm Description

Patients receive C3 complex/Bioperine PO BID for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial.

Patients receive placebo PO BID for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial.

Outcomes

Primary Outcome Measures

Mean change in peripheral blood levels of inflammatory cytokines
Interleukin (IL) 1beta, IL-6, IL-18, transforming growth factor-beta, and tumor necrosis factor-alpha will be assessed. Mean inflammatory cytokine changes in the treatment group will be compared to that of the control group. A two-sided two-sample unequal-variance t-test will be applied to compare the difference of the mean of changes at 12-months from the baseline measurement between the two arms, respectively. P-values from the test and the 95% confidence interval of the estimated difference will be reported for each of the inflammatory cytokines.
Mean change in symptom scores for clonal cytopenia of undetermined significance and low risk myelodysplastic syndrome patients
Symptoms scores will be assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3 (EORTC-QLQ-C30 version 3).This is a validated tool for assessing health-related quality of life in cancer patients. The questionnaire is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. Scores range from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.(no symptom) to 10 (worst possible symptom).
Mean change in symptom scores for myeloproliferative neoplasm (MPN) patients
MPN-related symptoms will be assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score. Possible scores range from 0 (no symptom) to 10 (worst possible symptom).

Secondary Outcome Measures

Change in the variant allele frequency of mutated clones
Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Change in the deoxyribonucleic acid methylation pattern
Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Change in peripheral blood cell counts
Peripheral blood cell counts will include absolute neutrophil count, hemoglobin, and platelets. Change in peripheral blood cell counts will be compared to pretreatment. Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Safety of curcumin in patients with CCUS/LR-MDS and symptomatic MPN
Will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Change in the rate of transfusion requirement measured
Will be measured by the number of units required per 8-week period. Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.

Full Information

First Posted
September 23, 2023
Last Updated
October 4, 2023
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT06063486
Brief Title
Curcumin to Improve Inflammation and Symptoms in Patients With Clonal Cytopenia of Undetermined Significance, Low Risk Myelodysplastic Syndrome, and Myeloproliferative Neoplasms
Official Title
A Phase 2, Double-blind, Randomized Study to Compare the Effect of Curcumin Versus Placebo on Inflammatory Cytokines, Symptoms and Disease Parameters in Clonal Cytopenia of Undetermined Significance (CCUS), Low-Risk Myelodysplastic Syndrome (LR-MDS), and Myeloproliferative Neoplasms (MPNs)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2, 2023 (Anticipated)
Primary Completion Date
October 2, 2025 (Anticipated)
Study Completion Date
October 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial evaluates how a curcumin supplement (C3 complex/Bioperine) changes the inflammatory response and symptomatology in patients with clonal cytopenia of undetermined significance (CCUS), low risk myelodysplastic syndrome (LR-MDS), and myeloproliferative neoplasms (MPN). Chronic inflammation drives disease development and contributes to symptoms experienced by patients with CCUS, LR-MDS, and MPN. Curcumin has been shown to have anti-inflammatory and anti-cancer properties and has been studied in various chronic illnesses and hematologic diseases.
Detailed Description
PRIMARY OBJECTIVES: I. To compare the change in inflammatory cytokine levels in study patients treated with curcumin versus placebo over a 12-month follow-up period. II. To compare the change in symptomatology in study patients treated with curcumin versus placebo over a 12-month follow-up period. SECONDARY OBJECTIVES: I. To investigate the effect on variant allele frequency (VAF) of baseline mutations in study patients treated with curcumin versus placebo. II. To investigate the effect on methylation patterns in study patients treated with curcumin versus placebo. III. To evaluate the effect on peripheral blood cells in study patients treated with curcumin versus placebo. IV. To assess the safety of curcumin for patients with CCUS/LR-MDS and symptomatic MPN who do not require disease-modifying therapy. EXPLORATORY OBJECTIVE: I. To investigate the correlation between inflammatory cytokine levels and symptom scores in study patients treated with curcumin versus placebo. OUTLINE: Patients are randomized to 1 of 2 arms. Arm I: Patients receive curcumin/demethoxycurcumin/bisdemethoxycurcumin-containing supplement (C3 complex)/piperine extract (standardized) (Bioperine) orally (PO) twice daily (BID) for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial. Arm II: Patients receive placebo PO BID for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up annually for up to 10 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clonal Cytopenia of Undetermined Significance, Essential Thrombocythemia, Myelodysplastic Syndrome, Myelofibrosis, Polycythemia Vera

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (C3 Complex/Bioperine)
Arm Type
Experimental
Arm Description
Patients receive C3 complex/Bioperine PO BID for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO BID for 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy at baseline and follow up, and collection of blood samples throughout the trial.
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood samples
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Aspiration
Intervention Description
Undergo bone marrow aspiration
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Biopsy
Other Intervention Name(s)
Biopsy of Bone Marrow, Biopsy, Bone Marrow
Intervention Description
Undergo bone marrow biopsy
Intervention Type
Dietary Supplement
Intervention Name(s)
Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement
Other Intervention Name(s)
Curcumin C3 Complex
Intervention Description
Given PO
Intervention Type
Dietary Supplement
Intervention Name(s)
Piperine Extract (Standardized)
Other Intervention Name(s)
Bioperine, Standardized Piperine Extract
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Placebo Administration
Other Intervention Name(s)
Sugar pills
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Mean change in peripheral blood levels of inflammatory cytokines
Description
Interleukin (IL) 1beta, IL-6, IL-18, transforming growth factor-beta, and tumor necrosis factor-alpha will be assessed. Mean inflammatory cytokine changes in the treatment group will be compared to that of the control group. A two-sided two-sample unequal-variance t-test will be applied to compare the difference of the mean of changes at 12-months from the baseline measurement between the two arms, respectively. P-values from the test and the 95% confidence interval of the estimated difference will be reported for each of the inflammatory cytokines.
Time Frame
At baseline, 3 months, and 12 months
Title
Mean change in symptom scores for clonal cytopenia of undetermined significance and low risk myelodysplastic syndrome patients
Description
Symptoms scores will be assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3 (EORTC-QLQ-C30 version 3).This is a validated tool for assessing health-related quality of life in cancer patients. The questionnaire is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. Scores range from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.(no symptom) to 10 (worst possible symptom).
Time Frame
At baseline, 3 months, 12 months
Title
Mean change in symptom scores for myeloproliferative neoplasm (MPN) patients
Description
MPN-related symptoms will be assessed using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score. Possible scores range from 0 (no symptom) to 10 (worst possible symptom).
Time Frame
At baseline, 3 months, 12 months
Secondary Outcome Measure Information:
Title
Change in the variant allele frequency of mutated clones
Description
Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Time Frame
After 12 months of treatment
Title
Change in the deoxyribonucleic acid methylation pattern
Description
Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Time Frame
After 12 months of treatment
Title
Change in peripheral blood cell counts
Description
Peripheral blood cell counts will include absolute neutrophil count, hemoglobin, and platelets. Change in peripheral blood cell counts will be compared to pretreatment. Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Time Frame
After 12 months of treatment
Title
Safety of curcumin in patients with CCUS/LR-MDS and symptomatic MPN
Description
Will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time Frame
Every 2 weeks for the first month of treatment, every month for the following 2 months, then every 3 months for a total of 12 months.
Title
Change in the rate of transfusion requirement measured
Description
Will be measured by the number of units required per 8-week period. Both parametric methods i.e., the two-sample t-test and the non-parametric Wilcoxon rank sum test (with no assumption on the distribution of the data) will be applied.
Time Frame
Up to 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >= 18 Eastern Cooperative Oncology Group (ECOG) =< 2 Ability to understand and willingness to sign a written informed consent Diagnosis of polycythemia vera (PV), essential thrombocytosis (ET) or myelofibrosis (MF) per World Health Organization (WHO) 2016 diagnostic criteria Presence of at least one symptom measurable using the MPN-/Symptom Assessment Form (SAF) with a severity greater than 3 MPN patients determined to have stable disease undergoing surveillance and unlikely to require initiation of new cytoreductive therapy (i.e., hydroxyurea, ruxotinib, interferon within the study period); patients on a stable dose of hydroxyurea for at least 6 months who meet the other inclusion/exclusion criteria may be included A diagnosis of CCUS or LR-MDS CCUS defined as persistent cytopenia for > 6 months (hemoglobin [Hgb] < 11.3 g/dL [7 mmol/L] in women and Hgb < 12.9 g/dL [8 mmol/L] in men, platelet < 150 x 10^9/L or neutrophils < 1.8 x 10^9/L), normal cytogenetics, presence of detectable MDS associated mutations and bone marrow morphology non-diagnostic of MDS or any other malignancies LR-MDS as defined by WHO 2016 diagnosis criteria Minimum baseline symptom score of 25 in the fatigue section of the symptom questionnaire Exclusion Criteria: Patients with intake of curcumin as a dietary supplement, including multivitamin and unwillingness to quit more than 24 hours before study start Patients with inability to understand and adhere to information given Patients receiving active treatment for another malignancy except with hormonal therapy for a malignancy considered to be in remission or growth factors (erythropoietin, granulocyte colony-stimulating factor [G-CSF] and luspatercept) Patients with intermediate or high-risk MDS Patients must not be pregnant or nursing Patients must not be on any oral or intravenous steroid or any other anti-inflammatories (ibuprofen > 200mg/week or 400mg/month, naproxen of any dose, > 325mg aspirin daily, any herbal anti-inflammatory concoction of any dose)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christine Duran
Phone
323-865-0371
Email
duran_c@med.usc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Casey L O'Connell, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Duran
Phone
323-865-0371
Email
duran_c@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Casey L. O'Connell, MD
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Duran
Phone
323-865-0371
Email
duran_c@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Casey L. O'Connell, MD

12. IPD Sharing Statement

Learn more about this trial

Curcumin to Improve Inflammation and Symptoms in Patients With Clonal Cytopenia of Undetermined Significance, Low Risk Myelodysplastic Syndrome, and Myeloproliferative Neoplasms

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