Effects of Nicotinamide in Patients With Chronic Lymphocytic Leukemia (CLL) With History of Non-melanoma Skin Cancers (NMSC)

This is an interventional treatment trial for Chronic Lymphocytic Leukemia Read More

Inclusion Criteria:

• Male or female subject aged ≥ 18 years.
• Histologically confirmed diagnosis of CLL per iwCLL criteria.
• History of ≥1 non-melanoma skin cancer (NMSC) diagnosed within the last 5 years

• Adequate liver function as defined as:

  • Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)

    ---Subjects with a known diagnosis of Gilbert's Syndrome: direct bilirubin ≤ 1.5x ULN

  • AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

• For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  --Women < 50 years of age:

  • Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
  • Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
  • Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

• Women ≥ 50 years of age:

  • Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
  • Had radiation-induced menopause with last menses >1 year ago; or
  • Had chemotherapy-induced menopause with last menses >1 year ago; or
  • Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.4.1.

Exclusion Criteria:

• Received chemotherapy (such as fludarabine, cyclophosphamide, bendamustine, or chlorambucil) within the last 6 months
• Received allogeneic stem cell transplant within the last 6 months.
• Taking nicotinamide or niacin supplements within the last 4 weeks.
• Taken acitretin or other oral retinoids within the past 6 months
• Received field treatment for AKs (topical use of 5-fluorouracil, imiquimod, diclofenac, retinoids; topical photodynamic therapy for AKs; laser resurfacing or chemical peel treatments for AKs) within the previous 4 weeks
• Large areas of confluent skin cancer at baseline preventing accurate assessment and counting of individual new skin cancers
• Need for ongoing carbamazepine use (possible interaction with nicotinamide)
• Severe GI malabsorption that may interfere with absorption of nicotinamide (per investigator's discretion)
• Patients with an expected life expectancy < 2 years
• Current evidence of uncontrolled, diabetes.
• Current evidence or history of peptic ulcer disease.
• Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.

Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.

- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), or hepatitis C.

Note: Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

• Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
• Subjects taking prohibited medications as described in Section 6.7.1. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.
• Have ever received a solid organ transplant and are currently taking immunosuppressive medications.