Hypomethylating Properties of Freeze-dried Black Raspberries (BRB) in Patients With Myelodysplastic Syndrome or Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN)

Study Overview
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Brief Summary
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This is a phase II, single-group pilot study to evaluate efficacy and methylation. This study's overarching aim is to evaluate the systemic effects of black raspberries in patients with myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm. Twenty-one patients with MDS will be treated with 25 gm (2x/day) of BRB powder taken orally.

Detailed Description
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STUDY RATIONALE: Hypomethylating agents (HMAs) such as azacitidine and decitabine are FDA approved therapies for MDS patients. Approximately 50% of patients respond to HMAs. In addition, HMAs have improved survival and quality of life of patients with MDS when compared with other therapies. Preclinical research shows black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice treated with BRBs. The aim of this study is to evaluate the hypomethylating properties of BRBs in patients with MDS or MDS/MPN for three cycles (one cycle = 28 days) of BRB supplementation. PRIMARY OBJECTIVE: To evaluate the potential hypomethylating effects of freeze-dried black raspberries (BRBs) in the peripheral blood of patients with myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) after three cycles of BRB administration. SECONDARY OBJECTIVE: To evaluate the toxicity of BRBs in patients with MDS or MDS/MPN. To evaluate the hematological response according to modified International Working Group (IWG) criteria (Appendix 2) in patients with MDS or MDS/MPN regardless of the initial blood count.

Official Title
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A Pilot Study to Investigate the Hypomethylating Properties of Freeze-dried Black Raspberries (BRB) in Patients With Myelodysplastic Syndrome or Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Freeze-Dried Black Raspberry Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a confirmed diagnosis of myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) proven by bone marrow biopsy/aspirate. Patients with cytopenias (blood cell counts lower than the institutional lower limit of normal within the eight weeks prior to the study) who are receiving or received: red blood cell transfusions observation platelet transfusions erythropoietin granulocyte colony-stimulating factors granulocyte-macrophage colony-stimulating factors hydrea Age >18 years. Predicted life expectancy of at least 12 weeks. Patients should be expected to stay on the same therapy for the period of the study. Patients who do not have an indication for and/or are unable to tolerate a hypomethylating agent are eligible for the study. Reproductive requirements: Female patients must meet one of the following: Postmenopausal for at least one year before the screening visit, or Surgically sterile, or If women are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 30 days after the last dose of study drug, AND Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.) Male patients, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following: Practice effective barrier contraception during the entire study treatment period and through 30 days after the last study drug dose, OR Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.) Ability to understand a written informed consent document, and the willingness to sign it. Exclusion Criteria: A potential subject who meets any of the following exclusion criteria is ineligible to participate in the study. Previously received hypomethylating agents. Allergy to black raspberries. Inability to swallow oral medication. Inability or unwillingness to comply with the BRB administration requirements. Uncontrolled intercurrent illness, including, but not limited to, symptomatic congestive heart failure, or psychiatric illness/social situations, that, in the treating investigator's discretion, would limit compliance with study requirements. Active infection not well controlled by antibacterial or antiviral therapy. Pregnant or lactating women. Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Intervention<br>Freeze-dried black raspberry powder administration. | Drug: Freeze-Dried Black Raspberry Powder<br>* 25 gm (2x/day) of freeze-dried black raspberry powder taken orally in 8 ounces of water for 12 weeks. If the patient is tolerating BRBs well and is benefiting from therapy, he or she will continue treatment for a total maximum of 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With Grade 3 or Higher Serious Adverse Events. | Adverse events assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0; patients will be evaluated every four weeks for toxicity. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Showing a Response. | The subject's best clinical response will be assessed based on the modified International Working Group response criteria while receiving BRBs. | Up to 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Black raspberries, MDS, Myelodysplastic Syndromes, hypomethylating effects, chemopreventive agent, BRB, pharmacokinetics