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

NCT04844528 | Recruiting Phase 2 DMC

• 1 other identifier: HCI141430
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Non-melanoma Skin Cancer (NMSC)

Outcome Measures

Primary Outcomes (1)

• Proportion 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.

  1 year

Secondary Outcomes (8)

• Number of new NMSC on skin exam after 1 year of treatment

  1 year

• proportion of CLL patients who develop squamous cell carcinoma (SCC) on skin exam after 1 and 2 years of treatment.

  up to 2 years

• proportion of CLL patients who develop basal cell carcinoma (BCC) on skin exam after 1 and 2 years of treatment.

  up to 2 years

• proportion of CLL patients who develop actinic keratosis (AK) on skin exam after 1 and 2 years of treatment.

  up to 2 years

• number of new NMSC developed during year 1 and year 2 for patients who receive placebo during the first year

  2 years

Study Arms (2)

Nicotinamide, Then Nicotinamide

EXPERIMENTAL

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

Placebo, Then Nicotinamide

EXPERIMENTAL

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; Drug: Placebo

Interventions

Nicotinamide DRUG

Oral nicotinamide 500 mg twice daily (BID).

Also known as: Niacinamide

Nicotinamide, Then Nicotinamide; Placebo, Then Nicotinamide

Placebo DRUG

Oral placebo twice daily for the first year.

Placebo, Then Nicotinamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Huntsman Cancer Institute: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Related Publications (17)

• Royle JA, Baade PD, Joske D, Girschik J, Fritschi L. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer. 2011 Sep 27;105(7):1076-81. doi: 10.1038/bjc.2011.313. Epub 2011 Aug 16.

  PMID: 21847118 BACKGROUND

• Kleinstern G, Rishi A, Achenbach SJ, Chaffee KR, Kay NE, Shanafelt TD, et al. Skin Cancers Among Chronic Lymphocytic Leukemia (CLL) Patients - the Effect of UV Radiation and CLL Clinical Characteristics. Blood. 2016;128(22):4772-.

  BACKGROUND

• Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia. Dermatol Surg. 2005 Jan;31(1):38-42; discussion 42. doi: 10.1111/j.1524-4725.2005.31006.

  PMID: 15720094 BACKGROUND

• Mehrany K, Weenig RH, Lee KK, Pittelkow MR, Otley CC. Increased metastasis and mortality from cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia. J Am Acad Dermatol. 2005 Dec;53(6):1067-71. doi: 10.1016/j.jaad.2005.08.055.

  PMID: 16310071 BACKGROUND

• Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015 Oct 22;373(17):1618-26. doi: 10.1056/NEJMoa1506197.

  PMID: 26488693 BACKGROUND

• Hampras SS, Locke FL, Chavez JC, Patel NS, Giuliano AR, Miller K, Gheit T, Tommasino M, Rollison DE. Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients. Leuk Lymphoma. 2018 Apr;59(4):911-917. doi: 10.1080/10428194.2017.1342822. Epub 2017 Jul 6.

  PMID: 28679298 BACKGROUND

• Park J, Halliday GM, Surjana D, Damian DL. Nicotinamide prevents ultraviolet radiation-induced cellular energy loss. Photochem Photobiol. 2010 Jul-Aug;86(4):942-8. doi: 10.1111/j.1751-1097.2010.00746.x. Epub 2010 May 13.

  PMID: 20492562 BACKGROUND

• Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis. 2009 Jan;30(1):101-5. doi: 10.1093/carcin/bgn248. Epub 2008 Nov 20.

  PMID: 19028705 BACKGROUND

• Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012 May;132(5):1497-500. doi: 10.1038/jid.2011.459. Epub 2012 Feb 2. No abstract available.

  PMID: 22297641 BACKGROUND

• Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA; European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia. 2000 Nov;43(11):1337-45. doi: 10.1007/s001250051536.

  PMID: 11126400 BACKGROUND

• Niren NM. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis. 2006 Jan;77(1 Suppl):11-6.

  PMID: 16871774 BACKGROUND

• Lampeter EF, Klinghammer A, Scherbaum WA, Heinze E, Haastert B, Giani G, Kolb H. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS Group. Diabetes. 1998 Jun;47(6):980-4. doi: 10.2337/diabetes.47.6.980.

  PMID: 9604880 BACKGROUND

• PubChem Compound Summary for CID 936, Nicotinamide: National Center for Biotechnology Information; [Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Nicotinamide.

  BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

• Glanz K, Yaroch AL, Dancel M, Saraiya M, Crane LA, Buller DB, Manne S, O'Riordan DL, Heckman CJ, Hay J, Robinson JK. Measures of sun exposure and sun protection practices for behavioral and epidemiologic research. Arch Dermatol. 2008 Feb;144(2):217-22. doi: 10.1001/archdermatol.2007.46.

  PMID: 18283179 BACKGROUND

• Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975 Aug;46(2):219-34.

  PMID: 1139039 BACKGROUND

• International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016 Jun;17(6):779-790. doi: 10.1016/S1470-2045(16)30029-8. Epub 2016 May 13.

  PMID: 27185642 BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lindsey Fitzgerald, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lindsey Gilstrap

CONTACT

801-213-4233; lindsey.gilstrap@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2021
• First Posted: April 14, 2021
• Study Start: February 25, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)