Myelodysplastic Syndromes
Conditions
Keywords
Black raspberries, MDS, Myelodysplastic Syndromes, hypomethylating effects, chemopreventive agent, BRB, pharmacokinetics
Brief summary
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
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.
Interventions
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.
Sponsors
Ehab L Atallah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dietary Intervention Freeze-dried black raspberry powder administration.
Freeze-Dried Black Raspberry Powder: 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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Dietary Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 4 / 18 |
Outcome results
Primary
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.
Time frame: Up to 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dietary Intervention | The Number of Patients With Grade 3 or Higher Serious Adverse Events. | 3 Participants |
Secondary
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.
Time frame: Up to 52 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dietary Intervention | The Number of Subjects Showing a Response. | 0 Participants |