Nicotinamide for Chronic Lymphocytic Leukemia and Skin Cancer

Overseen By Lindsey Gilstrap

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Nicotinamide, Niacin, Retinoids, others

Disqualifiers: Chemotherapy, Transplant, Diabetes, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

86 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take nicotinamide, niacin supplements, or certain other medications like acitretin within specific time frames before starting. If you're on prohibited medications, a washout period (time without taking them) is required before the trial.

What data supports the effectiveness of the drug nicotinamide for reducing the risk of skin cancer?

Research shows that taking nicotinamide (a form of vitamin B3) can lower the risk of non-melanoma skin cancers by 23% in people who have had these types of skin cancers before. Additionally, studies in mice have shown that nicotinamide can prevent skin cancer caused by UV light by boosting the skin's ability to repair DNA damage. ^{1 2 3 4 5}

Is nicotinamide safe for humans?

Nicotinamide (also known as niacinamide or Vitamin B3) has a favorable safety profile and is considered low-risk for use in humans, particularly for reducing the risk of non-melanoma skin cancers. ^{1 2 3 6 7}

How is the drug nicotinamide unique in treating chronic lymphocytic leukemia and skin cancer?

Nicotinamide (Vitamin B3) is unique because it can prevent skin cancer by reducing UV-induced immunosuppression and increasing skin NAD levels, which helps repair DNA damage. It is taken orally, making it a convenient option with a favorable safety profile for high-risk individuals. ^{2 3 4 5 7}

Research Team

Lindsey Fitzgerald

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia who've had non-melanoma skin cancer in the last 5 years. They must have normal liver function, agree to use contraception if of childbearing potential, and not be on certain medications or treatments that could interfere with the study.

Inclusion Criteria

I have had at least one non-melanoma skin cancer in the past 5 years.

I am not pregnant or I am post-menopausal.

I have been diagnosed with CLL or SLL according to the latest criteria.

Exclusion Criteria

I have not taken acitretin or other oral retinoids in the last 6 months.

You are not expected to live for more than 2 years.

I need to keep taking carbamazepine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Year 1

Participants receive either oral nicotinamide 500 mg twice daily or oral placebo for 1 year. Dermatologic examination and quantification of new NMSC at the end of the year.

52 weeks

Monthly visits for monitoring

Crossover Treatment Year 2

All participants receive Nicotinamide 500 mg BID for an additional year. Dermatologic examination and quantification of new NMSC at the end of the year.

52 weeks

Monthly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide
• Placebo

Trial Overview The trial tests whether Nicotinamide (a form of vitamin B3) taken orally can prevent new non-melanoma skin cancers in CLL patients. Participants are randomly given either Nicotinamide or a placebo for one year, then all receive Nicotinamide for another year while their skin health is monitored.

Participant Groups

Group I: Treatment: all patients Experimental Treatment 1 Intervention

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.

Group II: Arm 2: Placebo Placebo Group 1 Intervention

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.

Nicotinamide is already approved in United States, European Union for the following indications:

Approved in United States as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Approved in European Union as Nicotinamide for:

• Pellagra
• Acne vulgaris
• Rosacea
• Hyperpigmentation
• Hair thinning

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

In a study of 203 adults with a history of multiple non-melanoma skin cancers, patients were willing to accept a 23% reduction in skin cancer risk with a modest increase in cost, but they were not willing to accept a significant increase in severe infection risk associated with nicotinamide supplementation.

The findings suggest that while nicotinamide can reduce skin cancer risk, the potential for increased severe infections may deter patients from choosing this treatment, indicating a need for careful consideration of patient preferences in treatment recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. Boeri, M., Skelsey, MK., Schiro, JA., et al.[2023]

Oral niacin supplementation significantly reduces the incidence of skin cancer in mice exposed to UV radiation, with higher doses leading to greater reductions (from 68% in controls to 28% with 1.0% niacin).

Niacin enhances skin levels of NAD, which helps modulate important proteins involved in DNA damage response, and also prevents photoimmunosuppression, a key factor in UV-induced tumor formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. Gensler, HL., Williams, T., Huang, AC., et al.[2021]

Topical nicotinamide (vitamin B-3) effectively prevented UVB-induced immunosuppression in mice, which is crucial for the development of skin tumors, by starting treatment two weeks before UV exposure.

In a study involving UV-irradiated mice, nicotinamide reduced the incidence of skin tumors from 75% to 42.5%, demonstrating its potential as a preventive treatment against photocarcinogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide. Gensler, HL.[2013]

A systematic review of 29 trials involving 3039 patients found that oral nicotinamide significantly reduces the risk of skin cancers, including basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs), with a rate ratio of 0.50 compared to control.

While nicotinamide is effective in preventing skin cancers, it is associated with an increased risk of digestive adverse effects, suggesting that its use should be carefully considered, especially in healthy individuals or organ transplant recipients with a history of skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. Mainville, L., Smilga, AS., Fortin, PR.[2023]

A Phase 3 clinical trial showed that oral nicotinamide (NAM) is safe and effectively reduces the incidence of new non-melanoma skin cancers and actinic keratosis in high-risk individuals.

While NAM is recognized for its anti-aging properties and potential oncopreventive effects, the specific molecular and cellular mechanisms behind its ability to delay cancer development are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible mechanisms of cancer prevention by nicotinamide. Buqué, A., Bloy, N., Kroemer, G., et al.[2021]

Oral nicotinamide supplementation may help lower the risk of non-melanoma skin cancers, suggesting a potential preventive strategy for at-risk individuals.

Despite the current lack of definitive proof, nicotinamide is considered safe with a favorable side effect profile, making it a viable option for those at higher risk of skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide and Nonmelanoma Skin Cancers. Jamison, A., Malhotra, R.[2022]

Oral nicotinamide supplementation has been studied in five randomized controlled trials and other studies, showing a potential benefit in reducing the incidence of non-melanoma skin cancers (NMSC), particularly in high-risk individuals.

While current evidence is not definitive, nicotinamide has a favorable safety profile, making it a low-risk option for managing skin cancer risk, especially for those with a history of skin issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nicotinamide for non-melanoma skin cancers: A review. Hunt, SV., Jamison, A., Malhotra, R.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Possible mechanisms of cancer prevention by nicotinamide. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide and Nonmelanoma Skin Cancers. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Oral nicotinamide for non-melanoma skin cancers: A review. [2023]