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)

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

Experimental: 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.

Placebo Comparator: 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.

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