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

NCT ID: NCT03078855

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-07
• Study Completion Date: 2024-07-02

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Vitamin D plus rituximab

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.

Group Type: EXPERIMENTAL

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

vitamin D3 2,000 IU daily

Rituximab

Intervention Type: BIOLOGICAL

Administered weekly x 4

Placebo plus rituximab

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.

Group Type: PLACEBO_COMPARATOR

Rituximab

Intervention Type: BIOLOGICAL

Administered weekly x 4

Placebo

Intervention Type: OTHER

methylcellulose

Interventions

Vitamin D

vitamin D3 2,000 IU daily

Intervention Type: DIETARY_SUPPLEMENT

Rituximab

Administered weekly x 4

Intervention Type: BIOLOGICAL

Placebo

methylcellulose

Intervention Type: OTHER

Other Intervention Names

Cholecalciferol; Rituxan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Jonathan Friedberg

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Friedberg

Director, Wilmot Cancer Institute

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jonathan W. Friedberg, MD

Role: PRINCIPAL_INVESTIGATOR

James P. Wilmot Cancer Institute at University of Rochester

Locations

University of Miami

Miami, Florida, United States

Emory University, Winship Cancer Institute

Atlanta, Georgia, United States

University of Iowa

Iowa City, Iowa, United States

Washington University

St Louis, Missouri, United States

Weill Cornell Medical College

New York, New York, United States

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

Rochester, New York, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39677358 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01CA214890

Identifier Type: NIH

Identifier Source: secondary_id

View Link

66593

Identifier Type: -

Identifier Source: org_study_id