Safety and efficacy of Vitamin D3 supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial

Abstract

Objectives: The study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D₃ supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D₃ on complete haematological response (CHR) and its safety.

Design: Double-blind, placebo-controlled, exploratory randomised trial.

Setting: Tertiary care hospital in northern India.

Participants: Treatment-naive patients with chronic phase chronic myeloid leukaemia (n=62) aged >12 years were recruited from January 2020 to January 2021. Patients with progressive disease, pregnancy and hypercalcaemia were excluded.

Intervention: Oral vitamin D₃ supplementation (60 000 IU) or matched placebo was given once weekly for an initial 8 weeks along with imatinib after randomisation with 1:1 allocation ratio.

Primary and secondary outcome measures: The primary outcome was to compare EMR (defined as BCR-ABL1 transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D₃ levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Results: At baseline, 14.5% of the patients had normal vitamin D₃ levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D₃ group and 21 (75%) of the placebo group (OR 1.6, 95% CI 0.37 to 7.37, p=0.4). A significant difference in vitamin D₃ levels from baseline to the end of study was observed. Patients with vitamin D₃ supplementation did not achieve higher CHR in comparison with placebo (OR 1.3, 95% CI 0.25 to 7.23, p=1.0). Vitamin D3 levels were not significantly correlated with BCR-ABL1 levels. No dose-limiting toxicities were observed.

Conclusion: Vitamin D₃ levels were low among patients with CML-CP in this study. Vitamin D₃ supplementation with imatinib therapy did not have significant effect on EMR or CHR. Further clinical trials could be undertaken to assess the effective dosage and duration of vitamin D₃ supplementation in these patients.

Trial registration number: CTRI/2019/09/021164.

Keywords: clinical pharmacology; clinical trials; leukaemia; molecular aspects.