A Study to Evaluate the Effect of Vitamin D on PFS in Indolent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Despite strong evidence suggesting that vitamin D deficiency is associated with undesirable outcomes in patients with numerous cancers, there has never been a thorough study of vitamin D treatment in subjects undergoing treatment for cancer. The purpose of this study is to evaluate whether modification of vitamin D levels in the blood, through supplementation, can improve outcomes.

Official Title
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ILyAD (Indolent Lymphoma And Vitamin D) A Phase III Double Blind, Randomized Trial to Evaluate the Supplemental Effect of Vitamin D on Progression-free Survival in Patients With Low Tumor-burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab

Conditions
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Follicular Lymphoma, Small Lymphocytic Lymphoma, Marginal Zone Lymphoma, Mucosal-Associated Lymphoid Tissue Lymphoma

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Biological: Rituximab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each of the following criteria must be met in order for a patient to be considered eligible for registration: Biopsy proven (with hematopathology review at one of the participating sites to confirm correct histology in accordance with World Health Organization) indolent lymphoma to include the following diagnoses: Grade 1, 2, or 3a follicular lymphoma Small lymphocytic lymphoma (CLL excluded) Marginal zone lymphoma (nodal or splenic) Mucosal-associated lymphoid tissue Measurable disease defined by Lugano criteria No prior anti-lymphoma systemic therapy; prior radiation therapy allowed Age 18 or over Ann Arbor stages II, III or IV Patients with follicular lymphoma must have PET FDG-avid lymphoma and fulfill Low tumor burden by Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria: No mass > 7 cm < 3 distinct masses of greater than 3 cm No B symptoms No splenomegaly > 16 cm by computed tomography (CT) scan No risk of vital organ compression No leukemic phase > 5000/µl circulating lymphocytes (except for in patients with splenic marginal zone diagnosis) No cytopenias (platelets < 100,000/µl, hemoglobin < 10 g/dl, or absolute neutrophil count < 1500/µl) Exclusion Criteria: The following criteria will prevent inclusion of an inappropriate subject into the trial: Osteoporosis requiring prescription treatment Known symptomatic primary hyperparathyroidism Hypercalcemia defined as above the institutional normal range (corrected for albumin when albumin levels are below normal) History of calcium-related kidney stones Creatinine > 1.5X above upper limit of normal Women who are known to be pregnant or who plan to become pregnant while on rituximab treatment

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D plus rituximab<br> | Dietary Supplement: Vitamin D<br>* vitamin D3 2,000 IU daily<br>* Other names: Cholecalciferol;Biological: Rituximab<br>* Administered weekly x 4<br>* Other names: Rituxan;|
| Placebo Comparator: Placebo plus rituximab<br> | Biological: Rituximab<br>* Administered weekly x 4<br>* Other names: Rituxan;Other: Placebo<br>* methylcellulose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression or death | Mean time to death or progression defined as increase in lymphoma burden by at least 50% | Year three | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomization to death | Mean time to death | Year three | 
| Response to rituximab defined as reduction of lymphoma burden by at least 50% | Response is defined as reduction of lymphoma burden by at least 50% | 13 weeks |