Curcumin Supplement for Myelodysplastic Syndrome and Myeloproliferative Disorders

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Casey O'Connell, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Southern California

Must not be taking: Steroids, Anti-inflammatories

Disqualifiers: Intermediate/high-risk MDS, Pregnancy, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take curcumin supplements or certain anti-inflammatory drugs like steroids, high doses of ibuprofen, naproxen, or aspirin. If you're on a stable dose of hydroxyurea, you may still participate.

What data supports the effectiveness of the treatment Curcumin Supplement for Myelodysplastic Syndrome and Myeloproliferative Disorders?

Research suggests that curcumin, a natural compound from turmeric, may help treat myelodysplastic syndrome by targeting specific proteins involved in cancer cell growth and making cancer cells more sensitive to other treatments. It has shown potential in reducing cancer cell growth and enhancing the effects of other cancer drugs. ^{1 2 3 4 5}

Is curcumin safe for human use?

Curcumin, a component of turmeric, is generally well-tolerated in humans, with the most common side effects being nausea and diarrhea. While it has been used medicinally for thousands of years, caution is advised when used with chemotherapy agents due to potential interactions. ^{1 5 6 7 8}

How is the curcumin treatment different from other treatments for myelodysplastic syndrome?

Curcumin, a natural compound from turmeric, is unique because it targets multiple pathways involved in cancer development, including inhibiting EZH2, a protein linked to myelodysplastic syndrome. This multi-target approach is different from traditional treatments that often focus on a single target, potentially offering a broader anticancer effect with fewer side effects. ^{2 6 9 10 11}

Research Team

Casey O'Connell, MD

Principal Investigator

University of Southern California

Eligibility Criteria

Adults over 18 with certain blood disorders like polycythemia, thrombocytosis, or myelofibrosis who are stable and not likely to need new treatments soon. Also for those with clonal cytopenia or low-risk myelodysplastic syndrome, experiencing symptoms like fatigue. Not for pregnant/nursing individuals, those on steroids/anti-inflammatories, or taking curcumin supplements.

Inclusion Criteria

My condition is low-risk myelodysplastic syndrome.

My blood disorder is stable and I'm not expected to need new treatment soon.

I have been diagnosed with CCUS or low-risk MDS.

Exclusion Criteria

Patients must not be pregnant or nursing

I am not willing to stop taking curcumin supplements 24 hours before the study starts.

I am not on active treatment for another cancer, except hormone therapy for a cancer in remission.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive curcumin or placebo orally twice daily for 12 months. Bone marrow aspiration, biopsy, and blood sample collection are conducted throughout the trial.

12 months

Every 2 weeks for the first month, every month for the next 2 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with annual follow-ups for up to 10 years.

Up to 10 years

Treatment Details

Interventions

• Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement (Other)

Trial Overview This phase II trial tests if a curcumin supplement (with anti-inflammatory properties) can reduce inflammation and improve symptoms in patients with specific pre-leukemia conditions and other related blood disorders.

Participant Groups

Group I: Arm I (C3 Complex/Bioperine) Experimental Treatment 6 Interventions

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.

Group II: Arm II (placebo) Placebo Group 5 Interventions

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.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Dr. Samir A.

University of Southern California

Chief Executive Officer since 2024

PhD in Molecular Biology from the University of Southern California

Dr. Chung

University of Southern California

Chief Medical Officer since 2016

MD from UC San Diego

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Curcumin effectively inhibits the proliferation of hematopoietic progenitor cells (CFU-GM) and leukemic stem cells (WEHI-3B) in a dose-dependent manner, with IC50 values of 1.036 x 10(-5) mol/L for CFU-GM and 1.220 x 10(-6) mol/L for WEHI-3B.

The study demonstrates that curcumin has a stronger inhibitory effect on the proliferation of leukemic stem cells (WEHI-3B) compared to hematopoietic progenitor cells (CFU-GM), suggesting its potential as a therapeutic agent in leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of curcumin on the proliferation of murine CFU-GM and WEHI-3B cells]. Jiang, DZ., Xie, QY., Wang, QR.[2013]

Myelodysplastic syndromes (MDS) are complex disorders with significant biological diversity, making assessment and treatment challenging; however, new therapies targeting specific molecular pathways show promise for improving blood parameters and preventing disease progression.

Emerging treatments, such as farnesyl transferase inhibitors, receptor tyrosine kinase inhibitors, and more potent thalidomide analogs, have demonstrated encouraging results, indicating potential for durable benefits in MDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for myelodysplastic syndromes. Faderl, S., Kantarjian, HM.[2004]

Curcumin (CUR) enhances the effectiveness of arsenic trioxide (ATO) in treating myelodysplastic syndrome (MDS) and leukemia stem-like cells by increasing their sensitivity to ATO, as shown in experiments with SKM-1 and KG1a cell lines.

The combination treatment of CUR and ATO significantly increased apoptosis in these cells compared to either treatment alone, primarily by downregulating the survivin protein, which is known to inhibit cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells. Zeng, Y., Weng, G., Fan, J., et al.[2018]

Demethoxycurcumin (DMC) increased macrophage phagocytosis in leukemia mice, suggesting it may enhance immune response against cancer at certain doses.

While DMC did not significantly affect overall animal health or body weight, high doses led to decreased liver and spleen weights and reduced B and T cell proliferation, indicating a complex interaction with the immune system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demethoxycurcumin Promotes Macrophage Cell Population and Phagocytosis in WEHI-3 Cell-generated Leukemia BALB/c Mice In Vivo. Lin, YJ., Chen, CJ., Hsueh, SC., et al.[2021]

Clinical studies indicate that early intervention with curcumin, a compound from turmeric, may improve survival rates and delay disease progression in patients with early hematological malignancies, such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

These findings suggest that curcumin could be a promising therapeutic option for managing early-stage blood cancers, although further research is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-Cell Disorders and Curcumin. Golombick, T., Diamond, TH., Manoharan, A., et al.[2018]

The study identified multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of patients, showing that these cells can be targeted to predict the likelihood of cancer recurrence after treatment.

Curcumin/Piperine (C/P) extract demonstrated significant efficacy in suppressing MMCSCs by up to 64.71% in newly diagnosed patients, indicating its potential as a therapeutic option against multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer Stem Cells as a Prognostic Biomarker and Therapeutic Target Using Curcumin/ Piperine Extract for Multiple Myeloma. Mekkawy, SA., Abdalla, MS., Omran, MM., et al.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

[Effect of curcumin on the proliferation of murine CFU-GM and WEHI-3B cells]. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-cancer Effects of Curcumin on Myelodysplastic Syndrome through the Inhibition of Enhancer of Zeste Homolog-2 (EZH2). [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Novel therapies for myelodysplastic syndromes. [2004]

4. Greece pubmed.ncbi.nlm.nih.gov

Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Demethoxycurcumin Promotes Macrophage Cell Population and Phagocytosis in WEHI-3 Cell-generated Leukemia BALB/c Mice In Vivo. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical utility of curcumin extract. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The combination of dimethoxycurcumin with DNA methylation inhibitor enhances gene re-expression of promoter-methylated genes and antagonizes their cytotoxic effect. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

B-Cell Disorders and Curcumin. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Curcumin and cancer: barriers to obtaining a health claim. [2022]

11. Thailand pubmed.ncbi.nlm.nih.gov

Cancer Stem Cells as a Prognostic Biomarker and Therapeutic Target Using Curcumin/ Piperine Extract for Multiple Myeloma. [2023]