Niacinamide for the Treatment of Patients with Chronic Lymphocytic Leukemia with History of Non-melanoma Skin Cancer
This phase II trial investigates the effect of niacinamide in treating patients with chronic lymphocytic leukemia with history of non-melanoma skin cancer. Niacinamide is a form of vitamin B3. This trial aims to determine whether niacinamide may help reduce the risk of patients with chronic lymphocytic leukemia developing non-melanoma skin cancer.
Inclusion Criteria
- Male or female subject aged >= 18 years
- Confirmed diagnosis of CLL or small lymphocytic leukemia (SLL) patients per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
- History of >= 1 non-melanoma skin cancer (NMSC) diagnosed within the last 5 years
- Total Bilirubin =< 1.5 x institutional upper limit of normal (ULN) * Subjects with a known diagnosis of Gilbert’s syndrome: direct bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (Serum Glutamic Pyruvic Transaminase [SGPT]) =< 3 x 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
Exclusion Criteria
- Received cytotoxic chemotherapy (including 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 actinic keratosis (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 gastrointestinal (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 human immunodeficiency virus (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
- Known active uncontrolled infection.
- 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 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0 grade >= 3)
- Subjects taking prohibited medications. 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
Additional locations may be listed on ClinicalTrials.gov for NCT04844528.
Locations matching your search criteria
United States
Utah
Salt Lake City
PRIMARY OBJECTIVE:
I. To evaluate whether niacinamide (nicotinamide) can reduce the number of patients who develop one or more new non-melanoma skin cancer (NMSC) versus placebo in chronic lymphocytic leukemia (CLL) patients with a history of NMSC.
SECONDARY OBJECTIVES:
I. To assess the effect of oral nicotinamide on the number of new NMSC in patients with CLL who have previously been diagnosed with a NMSC.
II. To assess whether nicotinamide can reduce the number of patients who develop a squamous cell carcinoma (SCC) versus placebo in CLL patients with a history of NMSC.
III. To assess whether nicotinamide can reduce the number of subjects who develop a basal cell carcinoma (BCC) versus placebo in CLL patients with a history of NMSC.
IV. To evaluate whether nicotinamide can reduce the number of subjects who develop actinic keratosis (AK) versus placebo in CLL patients with a history of NMSC.
V. To evaluate whether nicotinamide can reduce the number of recurrent NMSC in the same patient between year 1 on placebo therapy and year 2 on nicotinamide therapy.
VI. To compare objective response rates (complete response [CR] + partial response [PR]) and CR rates between patients not on active CLL therapy who receive nicotinamide versus placebo.
VII. To compare overall response rates (complete response [CR] + partial response [PR]) and CR rates between patients not on active CLL therapy with and without mutations with deoxyribonucleic acid (DNA) mismatch repair who receive nicotinamide versus placebo.
VIII. To evaluate the safety and tolerability of each arm.
EXPLORATORY OBJECTIVES:
I. To compare markers of T-cell exhaustion in patients who do and do not develop a second NMSC.
II. To compare double-stranded DNA damage to CLL cells in patients receiving nicotinamide versus (vs) placebo.
III. To correlate the presence of human papilloma virus (HPV) in CLL cells and squamous cell carcinoma (SCC) cells.
IV. To distinguish subtypes of human papillomavirus (HPV) present in squamous cell carcinoma (SCC) cells.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive niacinamide orally (PO) twice daily (BID) for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study.
ARM II: Patients receive placebo PO BID for 1 year. Patients then crossover to Arm I and receive niacinamide PO BID for 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up for 36 months from the date of study therapy initiation.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationHuntsman Cancer Institute/University of Utah
Principal InvestigatorLindsey Fitzgerald
- Primary IDHCI141430
- Secondary IDsNCI-2021-08252
- ClinicalTrials.gov IDNCT04844528