Cholecalciferol in Newly Diagnosed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia With Vitamin D Deficiency

Study Overview
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Brief Summary
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This randomized pilot early phase I trial studies how well cholecalciferol works in treating patients with newly diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia with low levels of vitamin D (vitamin D deficiency). Cholecalciferol may increase levels of vitamin D and improve survival in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia receiving standard of care chemotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the 3 year progression-free survival (PFS), defined as time from the time of study entry of watch and wait or newly diagnosed non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) until relapse, progression, or death from any cause. SECONDARY OBJECTIVES: I. To evaluate changes in the levels of serum vitamin D levels during therapy with daily oral vitamin D supplementation (cholecalciferol). II. To evaluate the overall survival (OS), defined as time from the time of study entry of watch and wait patients or newly diagnosed NHL or CLL until death from any cause. OUTLINE: Patients with low levels of vitamin D are randomized to 1 of 2 arms and patients with normal levels are assigned to Arm III. ARM I: Patients receive high-dose cholecalciferol orally (PO) daily for 3 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive low-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive no intervention.

Official Title
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A Pilot Study of Vitamin D Replacement in Patients With Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia With Low Vitamin D Levels

Conditions
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Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, Untreated Chronic Lymphocytic Leukemia, Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed newly diagnosed or previously untreated (patients may be under no treatment ?wait and watch? or have received two cycles of chemotherapy or localized radiation therapy before going on this study) non-Hodgkin?s lymphoma or CLL Patients must have serum 25-hydroxyvitamin D (25[OH]D) drawn at time of enrollment; (NOTE: subjects currently taking vitamin D supplements are eligible for screening) Simultaneous participation in other therapeutic clinical trials will be allowed Patients must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts Exclusion Criteria: History of uncontrollable allergic reactions to vitamin D History of Paget?s disease Hypercalcemia Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the investigator?s opinion, may interfere with protocol adherence or a subject?s ability to give informed consent Inability to cooperate with the requirements of the protocol

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (high-dose cholecalciferol)<br>Patients receive high-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity. | Dietary Supplement: Cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>|
| Experimental: Arm II (low-dose cholecalciferol)<br>Patients receive low-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity. | Dietary Supplement: Cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>|
| No Intervention: Arm III (control)<br>Patients receive no intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The 3-year progression-free survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year progression-free survival of 45% using a one-sample logrank test following the method of Woolson (1981). | Time from the time of study entry of watch and wait or diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia until relapse, progression, or death from any cause, assessed at 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and serious events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | Will be described for the low dose and high dose groups and compared between groups using a Chi-square. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described for the low dose and high dose groups and compared between groups using a Chi-square. | Up to 30 days | 
| Overall survival | The 3-year overall survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year overall survival of 80% using a one-sample logrank test following the method of Woolson (1981). | Time from the time of study entry of watch and wait or newly diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia administered on trial until death from any cause, assessed at 3 years |