Lymphoma Non-Hodgkin, Vitamin D 25-Hydroxylase Deficiency
Conditions
Keywords
Non-Hodgkin lymphoma, Vitamin D deficiency, Overall survival, Efficacy
Brief summary
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
Interventions
DRUGHigh-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.
DRUGStandard 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.
Sponsors
Phramongkutklao College of Medicine and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Vitamin D Normalization by Day 21 | Day 21 (± 3 days) after the first dose of study medication | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | Up to 3 years | 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. |
| Progression-Free Survival (PFS) | Up to 3 years | 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. |
| Overall Survival (OS) | Up to 3 years | Overall survival is defined as the time from randomization to death from any cause. |
| Best Overall Response (BOR) | Through the completion of first-line immunochemotherapy, approximately 24 weeks | 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. |
| Change in Serum 25-Hydroxyvitamin D Level | Day 21 (± 3 days), Day 42 (± 3 days), Day 63 (± 3 days), and Day 126 (± 3 days) (end of treatment) | 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). |
| Incidence of Grade ≥ 3 Infections | From randomization through 30 days after the last dose of study treatment, approximately 22 weeks | Incidence of infections graded ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE), version 6.0. |
| Safety and Treatment-Related Toxicity | From randomization through 30 days after the last dose of study treatment, approximately 22 weeks | Safety and toxicity will be assessed based on the incidence of hypercalcemia, hypophosphatemia, and other adverse events, graded according to CTCAE version 6.0. |
Countries
Thailand
Contacts
CONTACTTanapun Thamgrang, MD
CONTACTNapakrit Tanpumiprated, MD
PRINCIPAL_INVESTIGATORTanapun Thamgrang
Division of Hematology, Department of Medicine, Phramongkutklao Hospital
Outcome results
None listed