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

Jonathan Friedberg

Status and phase: Completed; Phase 3

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

Treatments: Other: Placebo; Dietary Supplement: Vitamin D; Biological: Rituximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03078855

R01CA214890 (U.S. NIH Grant/Contract)

66593

Details and patient eligibility

About

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.

Enrollment: 211 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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211 participants in 2 patient groups, including a placebo group

Vitamin D plus rituximab

Experimental group

Description:

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.

Treatment:

Biological: Rituximab

Dietary Supplement: Vitamin D

Placebo plus rituximab

Placebo Comparator group

Description:

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.

Treatment:

Biological: Rituximab

Other: Placebo