Curcumin Supplement for Myelodysplastic Syndrome and Myeloproliferative Disorders

Recruiting at 2 trial locations

Overseen By Christine Duran

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Steroids, Anti-inflammatories

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a curcumin supplement can reduce inflammation and improve symptoms in individuals with certain blood disorders, such as clonal cytopenia of undetermined significance (CCUS), low-risk myelodysplastic syndrome (LR-MDS), and myeloproliferative neoplasms (MPN). Curcumin is known for its anti-inflammatory and anti-cancer properties. Participants will receive either the curcumin supplement or a placebo for 12 months to compare effects. Suitable candidates have been diagnosed with polycythemia vera, essential thrombocytosis, myelofibrosis, CCUS, or LR-MDS and experience significant symptoms that impact daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research shows that curcumin, the main ingredient in this supplement, is generally safe. Studies have found that curcumin helps treat chronic conditions like rheumatoid arthritis and inflammatory bowel disease without major safety concerns.

Curcumin has undergone testing in many clinical trials and is usually well-tolerated. Some studies even suggest it has a good safety record, with no serious side effects reported.

This supplement contains a specific curcumin complex studied for safety, and results suggest it does not cause significant harm. Overall, the evidence supports that this curcumin supplement is safe for use in similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using curcumin for treating myelodysplastic syndromes (MDS) and myeloproliferative disorders because it takes a natural approach, using compounds found in turmeric, which are known for their anti-inflammatory and antioxidant properties. Unlike standard treatments like chemotherapy or immunosuppressive therapies, this supplement could offer a gentler alternative with potentially fewer side effects. Curcumin's unique mechanism involves modulating multiple cellular pathways, which might help in reducing abnormal blood cell production and supporting healthier cell function. This novel approach could open up new possibilities for managing these conditions more holistically.

What evidence suggests that this curcumin supplement could be an effective treatment for myelodysplastic syndrome and myeloproliferative disorders?

Previous studies have shown that curcumin can reduce inflammation and fight cancer. Derived from turmeric, curcumin is known to be safe and effective in alleviating inflammation and symptoms in various long-term diseases. Research indicates it may benefit conditions like myelodysplastic syndrome and myeloproliferative disorders by reducing inflammation, a significant factor in these diseases. This trial will compare a curcumin-containing supplement, specifically the C3 Complex/Bioperine, with a placebo. Although more research is needed, these early findings suggest curcumin could help manage symptoms and improve the quality of life for patients with these conditions. ^{1 6 7 8 9}

Who Is on the Research Team?

Casey O'Connell, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Curcumin/ Demethoxycurcumin/Bisdemethoxycurcumin-containing Supplement

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.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

Curcumin effectively induces apoptosis and inhibits the growth of daunorubicin-resistant CD34+ acute myeloid leukemia (AML) cells, demonstrating its potential as a therapeutic agent in treating this challenging form of leukemia.

The study found that curcumin enhances the effectiveness of daunorubicin in resistant AML cells by down-regulating Bcl-2 expression, which is associated with increased susceptibility to chemotherapy, while sparing normal CD34+ hematopoietic progenitors from significant harm.

NCBI (Pubmed)

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. Rao, J., Xu, DR., Zheng, FM., et al.[2021]

The combination of dimethoxycurcumin (DMC) and the DNMT inhibitor decitabine (DAC) showed minimal cytotoxic effects on primary leukemia cells, indicating that this treatment may not be effective as a standalone therapy.

While the combination did not enhance DNA hypomethylation compared to DAC alone, it significantly increased histone acetylation, suggesting that the re-expression of tumor suppressor genes may occur through epigenetic changes rather than direct DNA methylation reversal.

NCBI (Pubmed)

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. Hassan, HE., Keita, JA., Narayan, L., et al.[2019]

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]

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]

Curcumin significantly inhibits cell proliferation and induces apoptosis in myelodysplastic syndrome (MDS) cell lines by reducing the expression of key epigenetic regulators like EZH2 and DNMT3a, as well as affecting histone modifications.

In a xenograft mouse model, curcumin demonstrated anti-cancer effects by decreasing EZH2 and associated histone marks, suggesting its potential as a therapeutic agent for MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-cancer Effects of Curcumin on Myelodysplastic Syndrome through the Inhibition of Enhancer of Zeste Homolog-2 (EZH2). Ma, L., Zhang, X., Wang, Z., et al.[2021]

Curcumin, a compound found in turmeric, has shown the ability to inhibit cancer cell growth and may help prevent or treat various types of cancers, including multiple myeloma and colorectal cancer, based on evidence from both animal studies and human trials.

Due to its ability to modulate multiple cell-signaling pathways, curcumin presents a promising alternative to traditional cancer therapies that often target a single pathway, potentially reducing costs and side effects associated with conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin and cancer: barriers to obtaining a health claim. Devassy, JG., Nwachukwu, ID., Jones, PJ.[2022]

Curcumin, the active component of turmeric, has shown promising anti-inflammatory and antineoplastic effects in preclinical studies, with early human trials indicating potential benefits for various conditions such as inflammatory bowel disease and rheumatoid arthritis.

Curcumin is generally well-tolerated, with mild side effects like nausea and diarrhea, but caution is advised regarding its interactions with chemotherapy agents, highlighting the need for further late-phase clinical trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of curcumin extract. Asher, GN., Spelman, K.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06063486

Study Details | NCT06063486 | Curcumin to Improve ... This phase II trial evaluates how a curcumin supplement (C3 complex/Bioperine) changes the inflammatory response and symptomatology in ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06976

Curcumin for Improving Inflammation and Symptoms in ... Curcumin has been shown to have anti-inflammatory and anti-cancer properties and has been studied in various chronic illnesses and hematologic diseases.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10111629/

Role of Turmeric and Curcumin in Prevention ... Curcumin, derived from turmeric, is safe, well tolerated, and effective in preventing and treating a wide range of chronic diseases.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/425815

Curcumin to Improve Inflammation and Symptoms in ... This phase II trial evaluates how a curcumin supplement (C3 complex/Bioperine) changes the inflammatory response and symptomatology in ...

5. mdsf.sparkcures.com mdsf.sparkcures.com/trial/1779/NCT06063486/description

Curcumin vs. Placebo This phase II trial evaluates how a curcumin supplement (C3 complex/Bioperine) changes the inflammatory response and symptomatology in patients with clonal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10061533/

Curcumin Formulations for Better Bioavailability: What We ... We extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases.

7. curcuminoids.com curcuminoids.com/gras/CurcuminC3ComplexGRASStatus.pdf

GRAS Notice 000460 The safety and toxicity data of turmeric and its extract are also extensive and thus, only relevant studies are briefly discussed in the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10629997/

Assessment of Safety Profile of Activated Curcumin C3 ... The present work was carried out to investigate the toxic effects of Activated Curcumin C3 Complex (AC3®) through the methods of acute, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2225411016302528

Review article Curcumin: An age-old anti-inflammatory and ... Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common ...