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

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

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.

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