Effects of Nicotinamide in Patients With Chronic Lymphocytic Leukemia With History of Non-melanoma Skin Cancers

November 25, 2025 updated by: University of Utah

Randomized Phase 2 Studying the Effects of Nicotinamide in Patients With Chronic Lymphocytic Leukemia (CLL) With History of Non-melanoma Skin Cancers (NMSC)

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

86

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute at University of Utah
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female subject aged ≥ 18 years.
  • Confirmed diagnosis of CLL or small lymphocytic leukemia (SLL) per iwCLL 2018 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.

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 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.

  • 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 (NCI CTCAE v5.0 Grade ≥ 3).
  • Subjects taking prohibited medications as described in study protocol. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nicotinamide, Then Nicotinamide
Consenting patients with CLL who have had at least one NMSC diagnosed in the past year will be randomized to receive oral nicotinamide 500 mg twice daily (BID) 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 be unblinded, and all patients will receive Nicotinamide 500 mg BID for an additional year.
Drug: Nicotinamide
Oral nicotinamide 500 mg twice daily (BID).
Other Names:
  • Niacinamide
Experimental: Placebo, Then Nicotinamide
Consenting patients with CLL who have had at least one NMSC diagnosed in the past year will be randomized to receive placebo twice daily (BID) 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 be unblinded, and all patients will receive Nicotinamide 500 mg BID for an additional year.
Drug: Nicotinamide
Oral nicotinamide 500 mg twice daily (BID).
Other Names:
  • Niacinamide
Drug: Placebo
Oral placebo twice daily for the first year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of CLL patients who develop a new NMSC after 1 year of nicotinamide therapy.
Time Frame: 1 year
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.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of new NMSC on skin exam after 1 year of treatment
Time Frame: 1 year
assess the effect of oral nicotinamide on the number of new NMSC in patients with CLL who have previously been diagnosed with a NMSC.
1 year
proportion of CLL patients who develop squamous cell carcinoma (SCC) on skin exam after 1 and 2 years of treatment.
Time Frame: up to 2 years
assess whether nicotinamide can reduce the number of patients who develop a SCC versus placebo in CLL patients with a history of NMSC.
up to 2 years
proportion of CLL patients who develop basal cell carcinoma (BCC) on skin exam after 1 and 2 years of treatment.
Time Frame: up to 2 years
assess whether nicotinamide can reduce the number of subjects who develop a BCC versus placebo in CLL patients with a history of NMSC
up to 2 years
proportion of CLL patients who develop actinic keratosis (AK) on skin exam after 1 and 2 years of treatment.
Time Frame: up to 2 years
evaluate whether nicotinamide can reduce the number of subjects who develop AK versus placebo in CLL patients with a history of NMSC
up to 2 years
number of new NMSC developed during year 1 and year 2 for patients who receive placebo during the first year
Time Frame: 2 years
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
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
Time Frame: up to 24 months
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
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
Time Frame: up to 24 months
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
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
Time Frame: up to 24 months
evaluate the safety and tolerability of each arm
up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

Huntsman Cancer Institute

Investigators

  • Principal Investigator: Lindsey Fitzgerald, MD, Huntsman Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2022

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

April 12, 2021

First Submitted That Met QC Criteria

April 12, 2021

First Posted (Actual)

April 14, 2021

Study Record Updates

Last Update Posted (Estimated)

December 3, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCI141430

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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