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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Mean change in peripheral blood levels of inflammatory cytokines
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/
排除标准
- •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)
研究组 & 干预措施
Arm I (C3 Complex/Bioperine)
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.
干预措施: Biospecimen Collection (Procedure)
Arm I (C3 Complex/Bioperine)
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.
干预措施: Bone Marrow Aspiration (Procedure)
Arm I (C3 Complex/Bioperine)
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.
干预措施: Bone Marrow Biopsy (Procedure)
Arm I (C3 Complex/Bioperine)
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.
干预措施: Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement (Dietary Supplement)
Arm I (C3 Complex/Bioperine)
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.
干预措施: Piperine Extract (Standardized) (Dietary Supplement)
Arm I (C3 Complex/Bioperine)
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.
干预措施: Questionnaire Administration (Other)
Arm II (placebo)
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.
干预措施: Biospecimen Collection (Procedure)
Arm II (placebo)
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.
干预措施: Bone Marrow Aspiration (Procedure)
Arm II (placebo)
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.
干预措施: Bone Marrow Biopsy (Procedure)
Arm II (placebo)
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.
干预措施: Placebo Administration (Drug)
Arm II (placebo)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Mean change in peripheral blood levels of inflammatory cytokines
时间窗: At baseline, 3 months, and 12 months
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
时间窗: At baseline, 3 months, 12 months
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
时间窗: At baseline, 3 months, 12 months
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).
次要结局
- Change in the variant allele frequency of mutated clones(After 12 months of treatment)
- Change in the deoxyribonucleic acid methylation pattern(After 12 months of treatment)
- Change in peripheral blood cell counts(After 12 months of treatment)
- Safety of curcumin in patients with CCUS/LR-MDS and symptomatic MPN(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(Up to 10 years)