High-Dose vs Standard Ergocalciferol for Vitamin D Normalization in Aggressive Non-Hodgkin Lymphoma

Safety and Efficacy of High-Intensity Loading Dose Versus Standard Weekly Dosing of Ergocalciferol (Vitamin D2) for Vitamin D Normalization in Patients With Newly Diagnosed Aggressive Non-Hodgkin Lymphoma: A Randomized, Open-Label, Controlled Trial

The goal of this clinical trial is to evaluate whether a high-intensity loading dose of ergocalciferol (vitamin D2) can normalize blood vitamin D levels more rapidly and safely than standard weekly dosing in patients with newly diagnosed aggressive non-Hodgkin lymphoma. The study will also assess the safety of both dosing strategies.

The main questions it aims to answer are:

• Does a high-intensity loading dose of ergocalciferol lead to faster normalization of serum 25-hydroxyvitamin D levels compared with standard weekly dosing?
• Are there differences in safety and adverse events between the two dosing strategies?

Researchers will compare a high-intensity loading dose regimen of ergocalciferol with a standard weekly dosing regimen to determine differences in vitamin D normalization and safety outcomes.

Participants will:

• Be randomly assigned to receive either a high-intensity loading dose or a standard weekly dose of ergocalciferol (vitamin D2)
• Receive standard first-line immunochemotherapy for aggressive non-Hodgkin lymphoma
• Have blood tests to monitor vitamin D levels, calcium, phosphate, and safety parameters at scheduled visits
• Be followed for treatment response, survival outcomes, and adverse events during and after therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma Non-Hodgkin; Vitamin D 25-Hydroxylase Deficiency
• Intervention / Treatment: Drug: High-Dose Loading Ergocalciferol; Drug: Standard Weekly Ergocalciferol

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tanapun Thamgrang, MD; Phone Number: 66859930142; Email: tanapun.tham@pcm.ac.th
• Study Contact Backup: Name: Napakrit Tanpumiprated, MD; Phone Number: 66881565102; Email: napakrich@hotmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Phramonkutklao Hospital
    • Contact: Tanapun Thamgrang, MD; Phone Number: 66859930142; Email: tanapun.tham@pcm.ac.th
    • Principal Investigator: Tanapun Thamgrang, MD
    • Sub-Investigator: Napakrit Tanpumiprated, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 20 years.
• Newly diagnosed aggressive non-Hodgkin lymphoma, confirmed by histopathological examination according to the WHO Classification of Haematolymphoid Tumours, 5th edition, with an indication for standard first-line chemoimmunotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
• Serum 25-hydroxyvitamin D level < 30 ng/mL within 14 days prior to randomization.
• Adequate organ function to receive full-dose standard chemotherapy.
• Ability to provide written informed consent.

Exclusion Criteria:

• Mild hypercalcemia (corrected Ca > 10.4 mg/dL)
• Hyperphosphatemia (PO4 > 4.5 mg/dL)
• History of urolithiasis associated with hypercalciuria or a diagnosis of primary hyperparathyroidism.
• Chronic kidney disease stage 4 or higher (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²).
• Inability to take oral medication, active gastrointestinal bleeding, or malabsorption syndrome.
• Pregnancy or breastfeeding.
• Prior systemic therapy for lymphoma.
• Ongoing tumor lysis syndrome requiring urgent treatment.
• Prior use of vitamin D supplements (ergocalciferol or cholecalciferol).

Withdrawal Criteria:

• Development of mild hypercalcemia.
• Development of mild hypophosphatemia.
• Development of hypervitaminosis D.
• Occurrence of severe adverse events (AEs) or side effects for which the investigator considers discontinuation of the study drug necessary for patient safety.
• Investigator's judgment that continued participation may pose a safety risk, such as the occurrence of serious infection, febrile neutropenia, or organ failure.
• Non-adherence to study medication, defined as cumulative vitamin D₂ intake of less than 80% of the expected cumulative dose at the time of serum vitamin D assessment.
• Participant withdrawal of consent to continue participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Dose Loading Ergocalciferol; Participants receive a high-dose loading regimen of ergocalciferol (vitamin D₂) for rapid normalization of serum vitamin D levels, in combination with standard first-line chemoimmunotherapy for aggressive non-Hodgkin lymphoma.	Drug: High-Dose Loading Ergocalciferol; Dose and Schedule: Loading phase: Ergocalciferol 20,000 IU orally once daily (1 capsule per dose), administered 1-2 hours before breakfast, for 7 consecutive days.; Intensified phase: Following the loading phase, ergocalciferol 20,000 IU orally three times per week (Monday, Wednesday, and Friday) for a total treatment duration of 6 weeks from the first dose.; Maintenance phase: After completion of the initial 6-week treatment period, ergocalciferol 20,000 IU orally once weekly (Monday) until completion of lymphoma treatment.; Maximum duration of vitamin D₂ administration: Up to 18 weeks from the first dose of ergocalciferol. Thereafter, vitamin D dosing may be adjusted at the discretion of the treating physician.
Active Comparator: Standard Weekly Ergocalciferol; Participants receive standard weekly dosing of ergocalciferol (vitamin D₂) for vitamin D normalization, in combination with standard first-line chemoimmunotherapy for aggressive non-Hodgkin lymphoma.	Drug: Standard Weekly Ergocalciferol; Dose and Schedule: Standard phase: Ergocalciferol 20,000 IU orally three times per week (Monday, Wednesday, and Friday), administered as 1 capsule per dose, 1-2 hours before breakfast, for a total duration of 6 weeks from the first dose.; Maintenance phase: After completion of the 6-week standard dosing period, ergocalciferol 20,000 IU orally once weekly (Monday) until completion of lymphoma treatment.; Maximum duration of vitamin D₂ administration: Up to 18 weeks from the first dose of ergocalciferol. Thereafter, vitamin D dosing may be adjusted at the discretion of the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Vitamin D Normalization by Day 21	Vitamin D normalization is defined as a serum 25-hydroxyvitamin D level ≥ 30 ng/mL. This outcome is assessed as a binary outcome (yes/no).	Day 21 (± 3 days) after the first dose of study medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	Event-free survival is defined as the time from randomization to the first occurrence of disease progression, relapse after response, initiation of new lymphoma therapy, or death from any cause.	Up to 3 years
Progression-Free Survival (PFS)	Progression-free survival is defined as the time from randomization to the first documented disease progression according to the Lugano 2014 criteria or death from any cause, whichever occurs first.	Up to 3 years
Overall Survival (OS)	Overall survival is defined as the time from randomization to death from any cause.	Up to 3 years
Best Overall Response (BOR)	Best overall response is defined as the best response achieved after completion of first-line immunochemotherapy, including complete response (CR) or partial response (PR), as assessed by PET-CT or CT scan according to the Lugano 2014 criteria.	Through the completion of first-line immunochemotherapy, approximately 24 weeks
Change in Serum 25-Hydroxyvitamin D Level	Changes in serum 25-hydroxyvitamin D levels will be compared between study arms and summarized as absolute change and central tendency measures (mean or median).	Day 21 (± 3 days), Day 42 (± 3 days), Day 63 (± 3 days), and Day 126 (± 3 days) (end of treatment)
Incidence of Grade ≥ 3 Infections	Incidence of infections graded ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE), version 6.0.	From randomization through 30 days after the last dose of study treatment, approximately 22 weeks
Safety and Treatment-Related Toxicity	Safety and toxicity will be assessed based on the incidence of hypercalcemia, hypophosphatemia, and other adverse events, graded according to CTCAE version 6.0.	From randomization through 30 days after the last dose of study treatment, approximately 22 weeks

Collaborators and Investigators

• Sponsor: Phramongkutklao College of Medicine and Hospital
• Investigators: Principal Investigator: Tanapun Thamgrang, Division of Hematology, Department of Medicine, Phramongkutklao Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Efficacy; Vitamin D deficiency; Non-Hodgkin lymphoma; Overall survival
• Additional Relevant MeSH Terms: Nutrition Disorders; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Avitaminosis; Deficiency Diseases; Malnutrition; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Vitamin D Deficiency; Vitamin D Hydroxylation-Deficient Rickets, Type 1B
• Other Study ID Numbers: Hemato-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to institutional policy and privacy concerns. Only aggregate data may be shared upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No