Calcitriol and Dexamethasone in Patients With Myelodysplastic Syndromes

Current therapeutic options for myelodysplastic syndromes (MDS) are limited and, aside from
bone marrow transplantation, none have proven superior to supportive measures alone.
Preclinical investigations have indicated the potential therapeutic role for vitamin D in
the treatment of MDS. However, because of the dose-limiting toxicity of hypercalcemia, past
clinical trials with vitamin D have been forced to utilize low doses, with promising but
inconsistent results.

This study utilizes a dosing schema of dexamethasone (Dex) and calcitriol (the active form
of vitamin D) that augments the therapeutic index of calcitriol, and allows for safe
administration of 5-10 times higher dose of calcitriol than previously has been used in
clinical trials for MDS. Patients will receive dexamethasone 4 times per week and calcitriol
3 times per week. This schedule will continue weekly until patients are off study. The dose
of calcitriol will be increased until the maximum tolerated dose (MTD) is determined.
History and physical examination, blood monitoring, urinary ultrasounds, and bone marrow
aspirations and biopsies will be used to assess disease response.

Inclusion criteria:

- Histologically confirmed refractory anemia (RA), RA with excess blasts (RAEB), RAEB
in transformation (RAEB-IT), or ringed sideroblasts (RARS)

- Evidence of cytopenia affecting at least 1 hematological cell lineage

- Adequate liver and renal function

- ECOG 0-2

- Expected survival of at least 12 weeks

Exclusion criteria:

- Symptomatic coronary artery disease

- Uncontrolled diabetes mellitus

- Uncontrolled and symptomatic glaucoma

- History of dangerous reactions to steroid therapy

- Chemotherapy or any hematopoietic growth factor therapy within the past 8 weeks

- History of nephrolithiasis

- Children

- Chronic myelomonocytic leukemia (CMML)