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)
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.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- Dietary SupplementCurcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement
Given PO
- Dietary SupplementPiperine Extract (Standardized)
Given PO
- DrugPlacebo Administration
Given PO
- OtherQuestionnaire Administration
Ancillary studies
Outcome measures
Primary
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.
Time frame: At baseline, 3 months, and 12 months
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).
Time frame: At baseline, 3 months, 12 months
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).
Time frame: At baseline, 3 months, 12 months
Secondary
Change in the variant allele frequency of mutated clones
Time frame: After 12 months of treatment
Change in the deoxyribonucleic acid methylation pattern
Time frame: After 12 months of treatment
Change in peripheral blood cell counts
Time frame: After 12 months of treatment
Safety of curcumin in patients with CCUS/LR-MDS and symptomatic MPN
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.
Change in the rate of transfusion requirement measured
Time frame: Up to 10 years
Eligibility criteria
Study locations (2)
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033