Research On Nicotinamide Riboside Supplement Support in MDS (ROSS Trial)

Prior treatment

• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV may participate.
• Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
  • Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure \> class 2, unstable angina, or myocardial infarction.
  • Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
• Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g. sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity.
• Any subject who is transfusion dependent and a candidate for MDS therapy such as erythroid stimulating agents, thrombopoietin receptor agonists, Lusparercept, Imetelstat or hypomethylating agents.

Other illness

• Subject is known to be positive for HIV with uncontrolled disease. HIV testing is not required.
• Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment.
• Subject has a history of other malignancies prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the breast or cervix uteri
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
  • Prostate cancer not requiring therapy beyond hormonal therapy
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
• Known or suspected hypersensitivity to nicotinamide riboside and pterostilbene.

Other

• Pregnant or breast-feeding females. A pregnancy test will be obtained at the time of screening if applicable.

• Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed procedures.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Be a male or female aged ≥ 18 years of age.
• For persons of reproductive potential, use of highly effective method(s) of contraception.
• Subject must have confirmation of high risk CCUS (defined by CHRS score) or the diagnosis of MDS in the lower risk category as defined by IPSS-M less than 0.
• Patients must have ECOG of ≤ 2
• Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.
• Subject must have adequate liver function as demonstrated by:
  • aspartate aminotransferase (AST) ≤ 3.0 × ULN
  • alanine aminotransferase (ALT) ≤ 3.0 × ULN
  • Unless due to Gilbert's syndrome, patients must have a total bilirubin ≤ 3 × ULN.
• Subject is informed that consumption of the following fruits is prohibited 3 days prior to the initiation of study treatment and throughout participation: grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit.