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)

Overview

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.

Interventions

• Procedure Biospecimen Collection
  Undergo collection of blood samples
• Procedure Bone Marrow Aspiration
  Undergo bone marrow aspiration
• Procedure Bone Marrow Biopsy
  Undergo bone marrow biopsy
• Dietary supplement Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement
  Given PO
• Dietary supplement Piperine Extract (Standardized)
  Given PO
• Drug Placebo Administration
  Given PO
• Other Questionnaire Administration
  Ancillary studies

Primary outcome measures

• Mean change in peripheral blood levels of 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 [Time frame: At baseline, 3 months, 12 months]
• Mean change in symptom scores for myeloproliferative neoplasm (MPN) patients [Time frame: At baseline, 3 months, 12 months]

Secondary outcome measures (5)

• 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

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 2 centers

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗