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

Jonathan Friedberg (Other)
Overall Status
Active, not recruiting ID
National Institutes of Health (NIH) (NIH), National Cancer Institute (NCI) (NIH)

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Vitamin D
  • Biological: Rituximab
  • Other: Placebo
Phase 3

Study Design

Study Type:
Actual Enrollment :
211 participants
Intervention Model:
Parallel Assignment
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
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
Actual Study Start Date :
Sep 7, 2017
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vitamin D plus rituximab

Dietary Supplement: Vitamin D
vitamin D3 2,000 IU daily
Other Names:
  • Cholecalciferol
  • Biological: Rituximab
    Administered weekly x 4
    Other Names:
  • Rituxan
  • Placebo Comparator: Placebo plus rituximab

    Biological: Rituximab
    Administered weekly x 4
    Other Names:
  • Rituxan
  • Other: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Time to progression or death [Year three]

      Mean time to death or progression defined as increase in lymphoma burden by at least 50%

    Secondary Outcome Measures

    1. Time from randomization to death [Year three]

      Mean time to death

    2. Response to rituximab defined as reduction of lymphoma burden by at least 50% [13 weeks]

      Response is defined as reduction of lymphoma burden by at least 50%

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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

    Contacts and Locations


    Site City State Country Postal Code
    1 University of Miami Miami Florida United States 33136
    2 Emory University, Winship Cancer Institute Atlanta Georgia United States 30322
    3 University of Iowa Iowa City Iowa United States 52242
    4 Washington University Saint Louis Missouri United States 63130
    5 Weill Cornell Medical College New York New York United States 10021
    6 James P. Wilmot Cancer Institute at University of Rochester Medical Center Rochester New York United States 14642
    7 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Jonathan Friedberg
    • National Institutes of Health (NIH)
    • National Cancer Institute (NCI)


    • Principal Investigator: Jonathan W. Friedberg, MD, James P. Wilmot Cancer Institute at University of Rochester

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Jonathan Friedberg, Director, Wilmot Cancer Institute, University of Rochester Identifier:
    Other Study ID Numbers:
    • 66593
    • R01CA214890
    First Posted:
    Mar 13, 2017
    Last Update Posted:
    Mar 8, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 8, 2022