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

NCT03078855 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 66593R01CA214890
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 7

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.

Conditions

Follicular Lymphoma; Small Lymphocytic Lymphoma; Marginal Zone Lymphoma; Mucosal-Associated Lymphoid Tissue Lymphoma

Outcome Measures

Primary Outcomes (1)

• Event Free Survival

  Event free survival (EFS) was defined as the time from randomization to lack of response at week 13, initiation of a new treatment, disease progression defined by Lugano criteria, or death, right-censored by time of last follow-up. Per Lugano criteria, progression is defined as a new FDG-avid lesion or an increase in intensity from baseline, an increase by \>= 50% in lesion diameters, a new lymph node \> 1.5 cm in any axis or a new extranodal site \> 1.0 cm.

  3 years

Secondary Outcomes (2)

• All-Cause Mortality

  Participants were followed for survival beginning on day 1 of treatment until study closure with a maximum follow-up of 64 months.

• Number of Participants With Treatment Response at 13 Weeks

  13 Weeks from the start of treatment

Study Arms (2)

Vitamin D plus rituximab

EXPERIMENTAL

Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and vitamin D3, 2000 IU orally once daily. Participants took vitamin D3 until lack of response at week 13, disease progression, or initiation of a new treatment.

Dietary Supplement: Vitamin D; Biological: Rituximab

Placebo plus rituximab

PLACEBO COMPARATOR

Rituximab was administered weekly x 4 (intravenous 375 mg/m\^2 or subcutaneous equivalent) per institutional standards and placebo orally once daily. Participants took placebo until lack of response at week 13, disease progression, or initiation of a new treatment.

Biological: Rituximab; Other: Placebo

Interventions

Vitamin D DIETARY_SUPPLEMENT

vitamin D3 2,000 IU daily

Also known as: Cholecalciferol

Vitamin D plus rituximab

Rituximab BIOLOGICAL

Administered weekly x 4

Also known as: Rituxan

Placebo plus rituximab; Vitamin D plus rituximab

Placebo OTHER

methylcellulose

Placebo plus rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (7)

University of Miami

Miami, Florida, 33136, United States

Location

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

James P. Wilmot Cancer Institute at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Friedberg JW, Brady MT, Strawderman M, Kahl BS, Lossos IS, Cohen JB, Reagan PM, Casulo C, Averill BL, Baran A, Sutamtewagul G, Barr PM, Leonard JP, Ashton JM, Strang JG, Vega F, Peterson DR, Nastoupil LJ. Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial. EClinicalMedicine. 2024 Nov 27;78:102959. doi: 10.1016/j.eclinm.2024.102959. eCollection 2024 Dec.

  PMID: 39677358 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

Vitamin D; Cholecalciferol; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Michael Brady, PhD
• Organization: University of Rochester

michael_brady@urmc.rochester.edu

585-275-5830

Study Officials

• Jonathan W. Friedberg, MD

  James P. Wilmot Cancer Institute at University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Wilmot Cancer Institute

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 13, 2017
• Study Start: September 7, 2017
• Primary Completion: July 21, 2023
• Study Completion: July 2, 2024
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data requests will be considered beginning in December 2024.

Locations

US (7)