Clinical trial NCT00057031: Study of High-Dose Pulse Administration DN-101 (Calcitriol) in Patients With Myelodysplastic Syndrome (MDS)
Official title: A Phase 2, Multicenter, Open Label Study of the Safety and Efficacy of High-Dose Pulse Administration DN-101 (Calcitriol) in Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Keywords: myelodysplastic syndrome
MDS
Lead sponsor: Novacea
Sponsor class: INDUSTRY
First posted: 2003-04-01
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of DN-101 (calcitriol) in patients with myelodysplastic syndrome who are dependent on repeat blood transfusions.

Detailed description: DN-101 is an experimental drug that has not been approved by the Food and Drug Administration (FDA). It is a newly formulated pill that contains high amounts of calcitriol, a naturally occurring hormone and the biologically active form of vitamin D. The natural vitamin D found in dairy products or in typical vitamin pills, must be chemically changed by the liver and kidney into calcitriol before it is biologically active. The body normally uses small amounts of calcitriol to regulate its blood calcium levels. However, for any possible therapeutic effect, MDS patients require much higher levels of calcitriol than the body can produce from dietary vitamin D. DN-101 provides MDS patients with high doses of calcitriol in a pill form.

Laboratory studies have demonstrated evidence supporting the use of calcitriol in MDS. High dose calcitriol slows the growth of leukemic cells (cancerous cells) and increases the growth of normal bone marrow cells. Some patients with MDS may have low levels of calcitriol in their bone marrow.

Clinical study results in patients with MDS have been mixed- some positive and some negative results. Elevated calcium in the blood occurred frequently and prevented the use of higher, more potentially therapeutic doses.

Novacea tested a new formulation of calcitriol, DN-101, in a Phase 1 study. In that study the maximum tolerated dose of DN-101 that did not cause high blood calcium levels when given weekly for several months was determined. That dose is within the range that is potentially therapeutic for MDS patients and will be used in this MDS study.

The purposes of this study are to determine if HDPA DN-101 treatment:

* increases the number of red blood cells, white blood cells, and platelets in the blood
* reduces the number of blood transfusions
* reduces the number of serious infections requiring antibiotics
* reduces the number of serious bleeding events
* improves fatigue

Eligibility criteria: * Diagnosis of low or intermediate-1 risk MDS
* Dependent on monthly blood transfusions
* No cancer within the last 5 years (cured skin cancer is allowed)
* No heart attack or stroke within the last 6 months
* No kidney stones within the last 5 years

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Clinical Research Consultants, Inc.
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital
state: Florida
city: Chicago
country: United States
facility: Rush Cancer Institute MDS Center
state: Illinois
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation, Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Memphis
country: United States
facility: Boston Baskin Cancer Group
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
References:
citation: Mellibovsky L, Diez A, Perez-Vila E, Serrano S, Nacher M, Aubia J, Supervia A, Recker RR. Vitamin D treatment in myelodysplastic syndromes. Br J Haematol. 1998 Mar;100(3):516-20. doi: 10.1046/j.1365-2141.1998.00598.x.
citation: Beer TM, Munar M, Henner WD. A Phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation. Cancer. 2001 Jun 15;91(12):2431-9.
citation: Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol. 2003 Jan 1;21(1):123-8. doi: 10.1200/jco.2003.05.117.