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 International Working Group (IWG) criteria (Appendix 2) in patients with MDS or MDS/MPN regardless of the initial blood count.

• Freeze-Dried Black Raspberry Powder (Drug): 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.

Primary outcomes

• The Number of Patients With Grade 3 or Higher Serious Adverse Events. [Up to 52 weeks]: 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.

Secondary outcomes

• The Number of Subjects Showing a Response. [Up to 52 Weeks]: The subject's best clinical response will be assessed based on the modified International Working Group response criteria while receiving BRBs.

Sex: All, ages: 18 Years to any

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.

Participant flow

Outcome results

• The Number of Patients With Grade 3 or Higher Serious Adverse Events. (Primary), Count of participants, Participants: Dietary Intervention 3
• The Number of Subjects Showing a Response. (Secondary), Count of participants, Participants: Dietary Intervention 0

Adverse events

Time frame: 52 weeks

Serious adverse events by term

Other adverse events by term

11 more terms not shown.

• Study Protocol and Statistical Analysis Plan (PDF, 2017-12-29)
• Informed Consent Form (PDF, 2018-05-08)

• Ehab Atallah, MD, Principal investigator, Medical College of Wisconsin