This is a randomized, phase II, double-blind, placebo-controlled trial with planned crossover to the intervention arm after 1 year. Consenting patients with CLL who have had at least one NMSC diagnosed in the past year will be randomized to receive either oral nicotinamide 500 mg twice daily (BID) for 1 year or oral placebo 1 tablet twice daily for 1 year. Patients will be stratified according to CLL therapy and the number of prior NMSC. At the end of 1 year, patients will undergo dermatologic examination and the number of new NMSC will be quantified. The number of patients who develop new NMSC in each arm will be documented. At this time, patients will be unblinded and all patients will receive Nicotinamide 500 mg BID for an additional year. At the end of this second year, patients will again undergo dermatologic examination, and the number of new NMSC will be quantified. The number of patients who develop NMSC will be documented. Skin biopsies will be taken for correlative studies. Enrollment will be split into two parts separated by an interim analysis. Part 1 will accrue 40 patients: 20 to each arm. After 40 patients have completed their 12 month visit an interim futility analysis will be conducted prior to recruiting more patients. The study will stop if the difference in the number of patients with NMSC between control and treatment arms is 0 or less (i.e., absolutely no evidence that the treatment is better than control). If the trial is not stopped, the investigators will proceed with Part 2 and recruit 46 more patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
86
Oral nicotinamide 500 mg twice daily (BID).
Oral placebo twice daily for the first year.
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States
RECRUITINGProportion of CLL patients who develop a new NMSC after 1 year of nicotinamide therapy.
evaluate whether nicotinamide can reduce the number of patients who develop one or more new NMSC versus placebo in CLL patients with a history of NMSC.
Time frame: 1 year
Number of new NMSC on skin exam after 1 year of treatment
assess the effect of oral nicotinamide on the number of new NMSC in patients with CLL who have previously been diagnosed with a NMSC.
Time frame: 1 year
proportion of CLL patients who develop squamous cell carcinoma (SCC) on skin exam after 1 and 2 years of treatment.
assess whether nicotinamide can reduce the number of patients who develop a SCC versus placebo in CLL patients with a history of NMSC.
Time frame: up to 2 years
proportion of CLL patients who develop basal cell carcinoma (BCC) on skin exam after 1 and 2 years of treatment.
assess whether nicotinamide can reduce the number of subjects who develop a BCC versus placebo in CLL patients with a history of NMSC
Time frame: up to 2 years
proportion of CLL patients who develop actinic keratosis (AK) on skin exam after 1 and 2 years of treatment.
evaluate whether nicotinamide can reduce the number of subjects who develop AK versus placebo in CLL patients with a history of NMSC
Time frame: up to 2 years
number of new NMSC developed during year 1 and year 2 for patients who receive placebo during the first year
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
Time frame: 2 years
objective response rate (the proportion of subjects achieving a complete response [CR] or partial response [PR]) and complete response rate as calculated per International Workshop on CLL (IWCLL) 2018 Criteria at Month 6, 12, 18, and 24
2.2.6 To compare objective response rates (CR + PR) and CR rates between patients not on active CLL therapy who receive nicotinamide versus placebo
Time frame: up to 24 months
objective response rate (the proportion of subjects achieving a CR or PR) and complete response rate as calculated per International Workshop on CLL (IWCLL) 2018 Criteria at Month 6, 12, 18, and 24
2.2.7 To compare overall response rates (CR+ partial PR) and CR rates between patients not on active CLL therapy with and without mutations with DNA mismatch repair who receive nicotinamide versus placebo
Time frame: up to 24 months
frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0 and iwCLL), seriousness, duration, and relationship to study treatment
evaluate the safety and tolerability of each arm
Time frame: up to 24 months
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