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

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 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.