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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Biospecimen Collection
  Undergo collection of blood samples
• Процедура Bone Marrow Aspiration
  Undergo bone marrow aspiration
• Процедура Bone Marrow Biopsy
  Undergo bone marrow biopsy
• Пищевая добавка Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement
  Given PO
• Пищевая добавка Piperine Extract (Standardized)
  Given PO
• Препарат Placebo Administration
  Given PO
• Другое Questionnaire Administration
  Ancillary studies

Первичные конечные точки

• Mean change in peripheral blood levels of inflammatory cytokines [Срок оценки: At baseline, 3 months, and 12 months]
• Mean change in symptom scores for clonal cytopenia of undetermined significance and low risk myelodysplastic syndrome patients [Срок оценки: At baseline, 3 months, 12 months]
• Mean change in symptom scores for myeloproliferative neoplasm (MPN) patients [Срок оценки: At baseline, 3 months, 12 months]

Вторичные конечные точки (5)

• Change in the variant allele frequency of mutated clones [Срок оценки: After 12 months of treatment]
• Change in the deoxyribonucleic acid methylation pattern [Срок оценки: After 12 months of treatment]
• Change in peripheral blood cell counts [Срок оценки: After 12 months of treatment]
• Safety of curcumin in patients with CCUS/LR-MDS and symptomatic MPN [Срок оценки: 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 [Срок оценки: Up to 10 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Los Angeles General Medical Center — Los Angeles
• USC / Norris Comprehensive Cancer Center — Los Angeles

Идентификаторы

NCT: NCT06063486 · 9L-23-1 · NCI-2023-06976 · 9L-23-1 · P30CA014089

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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