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

NCT ID: NCT04844528

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-25

Study Completion Date

2028-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia Non-melanoma Skin Cancer (NMSC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Nicotinamide

Intervention Type DRUG

Oral nicotinamide 500 mg twice daily (BID).

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.

Group Type EXPERIMENTAL

Nicotinamide

Intervention Type DRUG

Oral nicotinamide 500 mg twice daily (BID).

Placebo

Intervention Type DRUG

Oral placebo twice daily for the first year.

Interventions

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Nicotinamide

Oral nicotinamide 500 mg twice daily (BID).

Intervention Type DRUG

Placebo

Oral placebo twice daily for the first year.

Intervention Type DRUG

Other Intervention Names

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Niacinamide

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Huntsman Cancer Institute

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lindsey Fitzgerald, MD

Role: PRINCIPAL_INVESTIGATOR

Huntsman Cancer Institute

Locations

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Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lindsey Gilstrap

Role: CONTACT

801-213-4233

Facility Contacts

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Rachel Kingsford

Role: primary

801-585-0115

References

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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.

Reference Type BACKGROUND
PMID: 21847118 (View on PubMed)

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-.

Reference Type 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.

Reference Type BACKGROUND
PMID: 15720094 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16310071 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26488693 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28679298 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20492562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19028705 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22297641 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11126400 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 16871774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9604880 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 7165009 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18283179 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1139039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27185642 (View on PubMed)

Other Identifiers

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HCI141430

Identifier Type: -

Identifier Source: org_study_id

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