Vitamin D for Lymphoma

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must be taking: Vitamin D

Disqualifiers: Burkitt lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether vitamin D supplements can improve survival and tumor response in individuals with newly diagnosed lymphoma who have low vitamin D levels. Participants with aggressive lymphoma or untreated chronic lymphocytic leukemia (CLL) may be suitable, particularly if they are asymptomatic and plan to monitor their condition. The trial requires participants to take a vitamin D supplement regularly and track its effects over time. Participants must provide blood and tissue samples for research and attend follow-up appointments. As an unphased trial, this study offers a unique opportunity to contribute to understanding the potential benefits of vitamin D in lymphoma treatment.

Do I need to stop my current medications for the Vitamin D for Lymphoma trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you can participate in other therapies for your disease as long as they do not involve vitamin D.

Is there any evidence suggesting that cholecalciferol is likely to be safe for humans?

Research shows that cholecalciferol, a type of vitamin D, is generally safe for use. Studies have not identified any major harmful side effects. Vitamin D is often used to support overall health.

Past research indicates that individuals with low vitamin D levels often experience worse outcomes with certain cancers, suggesting potential benefits from vitamin D supplementation. However, strong evidence does not yet confirm that vitamin D significantly alters the course of diseases like lymphoma.

While vitamin D is safe, its precise benefits in cancer treatment remain under investigation. This trial seeks to explore these potential benefits further. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for lymphoma, which often involve chemotherapy and radiation, cholecalciferol, a form of vitamin D, offers a more natural approach by potentially boosting the immune system. Researchers are excited about this treatment because it targets vitamin D insufficiency, which has been linked to poorer outcomes in lymphoma patients. This method is unique because it involves a simple oral supplement, which may help enhance patients' overall health and potentially improve the effectiveness of other treatments.

What evidence suggests that cholecalciferol might be an effective treatment for lymphoma?

Research suggests that vitamin D, particularly as cholecalciferol, might help treat certain types of lymphoma. In this trial, patients with sufficient vitamin D levels will receive no intervention, while those with insufficient levels will receive cholecalciferol. Studies have shown that higher vitamin D levels are linked to better survival rates in patients with diffuse large B-cell lymphoma and T-cell lymphoma. Another study found that vitamin D can slow cancer cell growth and improve survival in B-cell lymphomas. However, vitamin D did not benefit patients with slow-growing lymphoma when combined with rituximab. Overall, vitamin D's role in treating lymphoma appears promising, especially for some aggressive types, but it may not be effective for all lymphoma patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Thomas E. Witzig, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for newly diagnosed patients with aggressive lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who can swallow capsules, are willing to return for follow-up and provide blood samples. They must have normal serum calcium levels and confirmed vitamin D insufficiency.

Inclusion Criteria

Willing to provide blood samples for correlative research purposes

I have been recently diagnosed with aggressive lymphoma or CLL/SLL.

I can swallow pills without any issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Vitamin D insufficient patients receive cholecalciferol orally once weekly for 12 weeks and then once monthly for a total of 36 months

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cholecalciferol

Trial Overview The study tests if cholecalciferol (a form of vitamin D) improves survival, tumor response, and delays treatment in cancer patients with low vitamin D. It's a partially randomized trial that includes laboratory biomarker analysis to monitor effects.

How Is the Trial Designed?

Group I: Treatment (cholecalciferol) Experimental Treatment 2 Interventions

Vitamin D sufficient patients receive no intervention. Vitamin D insufficient patients receive cholecalciferol PO once weekly for 12 weeks and then once monthly for a total of 36 months.

Cholecalciferol is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in European Union as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Canada as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Japan as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in China as Vitamin D3 for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Approved in Switzerland as Cholecalciferol for:

• Prevention and treatment of vitamin D deficiency
• Osteoporosis prevention
• Rickets prevention

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

This systematic review of 15 studies involving 4503 patients found that low vitamin D levels (below 20 ng/mL) are significantly associated with worse outcomes in lymphoid malignancies, including a nearly doubled risk of disease progression and lower overall survival rates.

Supplemental vitamin D may enhance the effectiveness of chemotherapy, particularly in patients with diffuse large B-cell lymphoma (DLBCL) undergoing R-CHOP treatment, suggesting that maintaining adequate vitamin D levels could be crucial for improving treatment responses and patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies. Potre, C., Borsi, E., Potre, O., et al.[2023]

In a study of 332 early-stage breast cancer survivors, only 30% had optimal vitamin D levels after cholecalciferol supplementation, indicating that current supplementation regimens may be insufficient for many patients.

Cholecalciferol supplementation did lead to increased levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D), but nearly 40% of patients still had levels below optimal, highlighting the need for better management of vitamin D levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D levels in Swiss breast cancer survivors. Baumann, M., Dani, SU., Dietrich, D., et al.[2018]

Vitamin D sufficiency may have a protective effect against malignancies, including non-Hodgkin lymphoma (NHL), through mechanisms like regulating cell growth and promoting cell differentiation.

Epidemiological studies suggest that increased sunlight exposure, which boosts vitamin D levels, is associated with a reduced risk of developing NHL, indicating that vitamin D status could play a role in this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and non-Hodgkin lymphoma risk in adults: a review. Kelly, JL., Friedberg, JW., Calvi, LM., et al.[2021]

In a study of 1127 lymphoma cases and matched controls with an average follow-up of 7.1 years, no overall protective association was found between plasma 25-hydroxyvitamin D (25(OH)D) levels and lymphoid cancer risk.

However, higher levels of 25(OH)D were linked to a significantly reduced risk of chronic lymphocytic leukemia (CLL), suggesting that while vitamin D may not protect against all lymphoid cancers, it could have a specific beneficial effect on CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition. Łuczyńska, A., Kaaks, R., Rohrmann, S., et al.[2023]

A study of 103 patients newly diagnosed with non-Hodgkin lymphoma, multiple myeloma, and chronic lymphocytic leukemia found that all participants had suboptimal serum vitamin D levels, indicating a potential area for intervention.

Severe vitamin D deficiency was particularly prevalent, affecting 81% of multiple myeloma patients, suggesting that addressing vitamin D levels could be important in the management of these blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D levels in patients with non-Hodgkin lymphoma/diffuse large B-cell lymphoma, chronic lymphocytic leukemia and multiple myeloma. Graklanov, V., Popov, V.[2021]

In a study of 270 lymphoid cancer cases among Finnish male smokers, higher levels of serum 25-hydroxyvitamin D (25(OH)D) were not generally associated with a reduced risk of overall lymphoid cancers or non-Hodgkin lymphoma (NHL).

However, for cases diagnosed within 7 years of blood draw, higher 25(OH)D levels showed a significant protective effect against NHL, suggesting that recent vitamin D exposure may play a role in short-term cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Lim, U., Freedman, DM., Hollis, BW., et al.[2021]

In a study of 332 newly diagnosed DLBCL patients, 92.8% were found to have insufficient vitamin D levels, and higher levels of bioavailable 25(OH)D were linked to significantly better progression-free survival and overall survival outcomes.

The findings suggest that bioavailable 25(OH)D could be a valuable prognostic biomarker for DLBCL patients, indicating that those with higher vitamin D levels may respond better to R-CHOP treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailable 25(OH)D level is associated with clinical outcomes of patients with diffuse large B-cell lymphoma: An exploratory study. Chen, P., Cao, Y., Duan, X., et al.[2021]

In two independent cohorts of untreated follicular lymphoma patients, low vitamin D levels were associated with worse progression-free survival (PFS) and overall survival, suggesting that vitamin D may influence lymphoma outcomes.

The study indicates that vitamin D deficiency could be a modifiable factor affecting survival in follicular lymphoma, warranting further research into the potential benefits of vitamin D supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies. Kelly, JL., Salles, G., Goldman, B., et al.[2022]

In a study of 251 patients with peripheral T-cell lymphoma (PTCL) and extranodal natural killer/T-cell lymphoma (ENKTL), vitamin D deficiency was found to significantly impact survival outcomes, particularly in patients with ENKTL.

Patients with ENKTL who had low serum levels of vitamin D (25-hydroxyvitamin D) showed poorer survival rates, while this association was not observed in PTCL patients, suggesting a specific link between vitamin D levels and ENKTL prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency is associated with inferior survival of patients with extranodal natural killer/T-cell lymphoma. Kim, SJ., Shu, C., Ryu, KJ., et al.[2022]

Vitamin D3 has shown potential as an antitumor agent in a mouse model of lymphoma, significantly reducing chromosomal aberrations and sister chromatid exchanges, which are markers of genetic damage.

Mice treated with Vitamin D3 experienced nearly double the survival time compared to untreated controls (68 days vs. 37 days), indicating its efficacy in combating tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticlastogenic potential of 1alpha,25-dihydroxyvitamin D3 in murine lymphoma. Sarkar, A., Saha, BK., Basak, R., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10137018/

A Systematic Review Assessing the Impact of Vitamin D ... The study found a significant association between vitamin D levels and survival for diffuse large B-cell lymphoma (DLBCL) and T-cell lymphoma ( ...

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00538-8/fulltext

Vitamin D in patients with low tumor-burden indolent non ... As tested in this study, there is no benefit to routine vitamin D supplementation in patients with indolent lymphoma treated with rituximab.

3. mdpi.com mdpi.com/1718-7729/32/3/135

Influence of Vitamin D and Its Analogues in Type-B ... Vitamin D inhibits cancer cell growth and enhances anti-proliferative effects. Higher levels of VitD are linked to better survival in B-cell lymphomas.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123052102

Ilyad: A Phase III Double Blind, Randomized Trial ... We observed no statistically significant benefit of vitamin D supplementation in patients with indolent lymphoma treated with rituximab in this phase III, ...

5. youtube.com youtube.com/watch?v=UgpZ-TylYAM

Mayo Clinic Study Finds Vitamin D Associated with Survival in ... The researchers study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2953973/

Vitamin D Insufficiency and Prognosis in Non-Hodgkin's ... In addition to risk of developing malignancy, there are recent data that suggest low 25(OH)D levels at diagnosis may be associated with poorer prognosis in ...