Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

December 26, 2025 updated by: Mayo Clinic

Effect of Vitamin D Replacement on Tumor Response and Survival Parameters for Vitamin D Insufficient Patients With Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated diffuse large B-cell lymphoma (DLBCL) can improve event free survival at 12 months to be equivalent to that of a control population of vitamin D sufficient patients. (Study I) II. To assess the percentage of patients requiring treatment with conventional therapy at 36 in months in vitamin D insufficient patients with early stage chronic lymphocytic leukemia (CLL) being managed with observation who undergo vitamin D replacement. (Study II)

SECONDARY OBJECTIVES:

I. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on overall survival. (Study I) II. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on event free survival. (Study I) III. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated T cell lymphoma on event free and overall survival. (Study I) IV. To assess the effect of vitamin D replacement in vitamin D insufficient CLL patients on Bio-r response rate and overall response rate. (Study II) V. To assess time to treatment and overall survival in vitamin D insufficient CLL patients who received vitamin D replacement. (Study II)

TERTIARY OBJECTIVES:

I. To study immune effector cells (lymphocytes, monocytes), serum cytokines, and tumor cells from vitamin D deficient and sufficient patients to learn the effects of vitamin D on both tumor cells and the patient's immune system. (Study I-II)

OUTLINE:

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

After completion of study treatment, patients are followed up for 2 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
565

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic in Arizona
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University/Winship Cancer Institute
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Newly diagnosed aggressive lymphoma or CLL/small lymphocytic lymphoma (SLL) that meets disease specific criteria below:

  • Study 1 - Aggressive lymphoma

    • Newly diagnosed de-novo DLBCL or primary mediastinal B-cell lymphoma that will be treated with an anthracycline-containing regimen (rituximab-cyclophosphamide, doxorubicin hydrochloride, prednisone [R-CHOP] or equivalent); patients with composite lymphomas can also be enrolled as long as they have large cell component and will be treated with an anthracycline; in addition, patients with "B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma" or post-transplant DLBCL are also eligible as long as they meet other criteria; patients with typical Burkitt lymphoma are not eligible

      • NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; the patient is permitted to participate in any other therapeutic therapy for their disease as long as it does not concern vitamin D; patients can begin their chemotherapy while awaiting vitamin D results and treatment arm assignment or

    • Newly diagnosed untreated peripheral T-cell non-Hodgkin lymphoma (NHL) that will be treated with chemotherapy; NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; this includes the following disease types:

      • Peripheral T cell lymphoma, unspecified
      • Anaplastic large cell lymphoma (T and null cell type)
      • Extranodal NK/T-cell lymphoma, nasal type
      • Enteropathy-type T-cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Subcutaneous panniculitis-like T-cell lymphoma
      • Angioimmunoblastic T-cell lymphoma
      • Anaplastic large cell lymphoma - primary cutaneous type and
    • Willing to provide tissue for correlative research purposes

  • Study 2 - CLL/SLL

    • Newly diagnosed (< 12 months from pre-registration on this study) CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of:

      • Biopsy-proven small lymphocytic lymphoma

      • Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:

        • Peripheral blood lymphocyte count of > 5,000/mm^3; if present, prolymphocytes should be < 55%

        • Immunophenotyping consistent with CLL defined as:

          • The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
          • Dim surface immunoglobulin expression
          • Restricted surface kappa or lambda light chain expression
        • Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(immunoglobulin H [IgH]/cyclin D 1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
    • Rai stage 0 or 1
    • Previously untreated
    • Asymptomatic with the plan for observation
    • Life expectancy of at least 24 months
    • Willing to provide tissue for correlative research purposes
  • Both Studies:
  • Capable of swallowing intact study medication capsules
  • Serum calcium < 11 mg/dL; note: patients with hypercalcemia can be enrolled after the calcium is corrected with standard of care treatments

  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

    • Note: During the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Willing to provide blood samples for correlative research purposes
  • Vitamin D level (25 hydroxy D2 + hydroxyl D3) confirmed by central laboratory review

Exclusion Criteria:

  • Patients with Burkitt lymphoma or any patient receiving rituximab-cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate / ifosfamide, etoposide, high-dose cytarabine (R- CODOXM/IVAC)
  • Patients who previously had indolent lymphoma and now at a separate episode have large cell NHL (i.e. transformation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (cholecalciferol)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Dietary supplement: Cholecalciferol
Given PO
Other Names:
  • Vitamin D3
  • 9,10-Secocholesta-5,7,10(19)-trien-3-ol
  • Calciol
  • Delsterol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event free survival (EFS) (Study I)
Time Frame: Time from study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed at 12 months
The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.
Time from study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed at 12 months
Treatment free status (Study II)
Time Frame: At 36 months
The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.
At 36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bio-R response rate (Study II)
Time Frame: Up to 5 years
Bio-R response rate will be calculated as the number of patients with Bio-R response divided by the number of evaluable patients. If a sufficient number of Bio-R responses are seen, differences in Bio-R rate between the two study groups will be evaluated using Fisher's exact test.
Up to 5 years
EFS time (Study I)
Time Frame: From study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed up to 5 years
The distribution of event-free survival time in each group will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models.
From study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed up to 5 years
OS (Study II)
Time Frame: From registration to death due to any cause, assessed up to 5 years
The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].
From registration to death due to any cause, assessed up to 5 years
Overall response rate (Study II)
Time Frame: Up to 5 years
Exact binomial 95% confidence intervals for the true overall response rate will be calculated. If a sufficient number of responses are seen, differences in overall response rate between the two study groups will be evaluated using Fisher's exact test.
Up to 5 years
Overall survival (OS) time (Study I)
Time Frame: From registration to death due to any cause, assessed up to 5 years
The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].
From registration to death due to any cause, assessed up to 5 years
Time to first treatment (Study II)
Time Frame: From study registration to initiation of anti-CLL therapy, assessed up to 5 years
The distribution of time to first treatment will be estimated using the method of Kaplan-Meier. Differences between the two study groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].
From study registration to initiation of anti-CLL therapy, assessed up to 5 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gene expression profiles
Time Frame: Baseline
Analysis will be primarily hypothesis generating and of a discovery nature. Gene expression will be compared to on-study vitamin D levels using Spearman correlation to look for associations between genes and Vitamin D. Gene expression will also be compared to polymorphisms in VDR using logistic regression to look for associations of host-genetics in the VDR region and general gene function in tumor.
Baseline
Immune effector cell levels
Time Frame: Up to 36 months
On-study regulatory T cells (Treg) and monocyte levels will be compared between sufficient and insufficient patients using Wilcoxon rank sum tests for each subtype. The pre and post-replacement levels will be assessed in CLL patients receiving replacement to look for a reduction in Tregs and monocytes, using a one-sample t-test on the difference testing for a mean of zero.
Up to 36 months
Serum cytokine profile
Time Frame: Up to 36 months
A five-parameter regression formula will be used to calculate the sample concentrations from the standard curves and a change of 50% from the baseline value will be considered significant. Changes in all 30 cytokines in the kit will be evaluated with a focus on the tumor specific cytokines. In patients with abnormal cytokines, the pre and post-replacement cytokine level will be compared in patients receiving replacement to similar timepoints in patients not receiving replacement. The change in cytokine levels (post-pre) will be evaluated between the two groups using Wilcoxon rank sum tests.
Up to 36 months
Vitamin D metabolism single nucleotide polymorphisms (SNPs)
Time Frame: Up to 36 months
All analyses will be performed separately for each lymphoma subtype. Individual vitamin D receptor (VDR) SNPs will be evaluated using a co-dominant model. Principal components will be used to generate a gene level assessment of VDR variability. Host genetic VDR markers will be compared to onstudy vitamin D levels to look for association between VDR polymorphisms and vitamin D stores using logistic regression. Host genetic VDR markers will be compared to outcome (time to first treatment [TFT], EFS, OS) using Cox regression models.
Up to 36 months
Vitamin D receptor expression on tumor cells
Time Frame: Baseline
The results will be expressed as present or absent. In the case of immunohistochemistry for DLBCL, expression may be graded as 0-3+. In the case of CLL, the % cells positive will be reported. VDR expression from the tumor will be reported using summary tables. Expression will be compared with outcome (TFT, EFS, OS) using Cox models to examine if VDR expression is prognostic in these tumors. VDR expression will also be compared to polymorphisms in VDR using logistic regression or chi-square tests to look for associations of host-genetics in the VDR region and VDR function in tumor.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mayo Clinic

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas E. Witzig, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 6, 2013

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 6, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2013

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LS1293 (Other Identifier: Mayo Clinic)
  • NCI-2013-00037 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P50CA097274 (U.S. NIH Grant/Contract)
  • 12-007862 (Other Identifier: Mayo Clinic Institutional Review Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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