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

 1. To evaluate the toxicity of BRBs in patients with MDS or MDS/MPN.

 2. 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.
Inclusion Criteria:

 1. Patients must have a confirmed diagnosis of myelodysplastic syndrome or
 myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) proven by bone marrow
 biopsy/aspirate.

 2. 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

 3. Age >18 years.

 4. Predicted life expectancy of at least 12 weeks.

 5. Patients should be expected to stay on the same therapy for the period of the study.

 6. Patients who do not have an indication for and/or are unable to tolerate a
 hypomethylating agent are eligible for the study.

 7. 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.)

 8. 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.

 1. Previously received hypomethylating agents.

 2. Allergy to black raspberries.

 3. Inability to swallow oral medication.

 4. Inability or unwillingness to comply with the BRB administration requirements.

 5. 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.

 6. Active infection not well controlled by antibacterial or antiviral therapy.

 7. Pregnant or lactating women.

 8. 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.