Vitamin D for Lymphoma

Recruiting at 4 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

565 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Cholecalciferol (Vitamin D3) for treating lymphoma?

Research suggests that higher vitamin D levels are linked to better survival outcomes in certain types of lymphoma, such as follicular lymphoma and extranodal natural killer/T-cell lymphoma. This implies that maintaining adequate vitamin D levels might improve prognosis in these conditions. ^{1 2 3 4 5}

Is Vitamin D3 safe for humans?

Vitamin D3 (Cholecalciferol) is generally considered safe for humans and is widely used as a supplement. It has been studied for its potential benefits in various conditions, including cancer, and no significant safety concerns have been reported in the research provided. ^{2 3 6 7 8}

How does the drug Cholecalciferol differ from other treatments for lymphoma?

Cholecalciferol (Vitamin D3) is unique because it focuses on addressing vitamin D deficiency, which has been linked to poorer survival outcomes in certain types of lymphoma, like extranodal natural killer/T-cell lymphoma. Unlike traditional chemotherapy or radiation, this drug aims to improve patient outcomes by potentially enhancing vitamin D levels, which may have protective effects against lymphoma. ^{2 4 7 9 10}

What is the purpose of this trial?

This partially randomized clinical trial studies cholecalciferol in improving survival in patients with newly diagnosed cancer with vitamin D insufficiency. Vitamin D replacement may improve tumor response and survival and delay time to treatment in patients with cancer who are vitamin D insufficient.

Research Team

Thomas E. Witzig, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies. [2023]

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

Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency is associated with inferior survival of patients with extranodal natural killer/T-cell lymphoma. [2022]

5. England 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. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Anticlastogenic potential of 1alpha,25-dihydroxyvitamin D3 in murine lymphoma. [2019]

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

A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Vitamin D levels in Swiss breast cancer survivors. [2018]

9. England 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Vitamin D and non-Hodgkin lymphoma risk in adults: a review. [2021]