Clinical trial NCT00715247: Polycythemia Vera, Myelofibrosis and Essential Thrombocythemia: Identification of PV, MF & ET Genes
Official title: Polycythemia Vera, Myelofibrosis and Essential Thrombocythemia: Identification of PV, MF & ET Genes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Keywords: Myeloproliferative Disorders
Hematological Malignancies
Polycythemia Vera
Essential Thrombocythemia
Myelofibrosis
Genetics
Chronic Leukemia
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Myeloproliferative Disorders-Research Consortium
name: National Cancer Institute (NCI)
First posted: 2008-07-15
Enrollment: 726
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients suspected to have one of the following blood disorders: polycythemia vera, myelofibrosis or essential thrombocythemia.

Brief summary: The purpose of this project is to find genes whose mutations cause Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis.

Detailed description: Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), also known as the Philadelphia Chromosome negative myeloproliferative disorders (MPDs), are not congenital, but acquired. The purpose of this project is to find genes whose mutations cause these disorders, as well as improve diagnostic measures for these diseases. When this is accomplished new therapies to control and eventually cure the disease can be designed.

All subjects will be asked to donate 4-6 teaspoons of blood. On occasion, if the blood cells from a particular sample do not grow well and the DNA from that sample is used up or other tests are needed, we may ask to collect additional samples. In patients who have undergone a bone marrow biopsy as part of their clinical evaluation, we will test the reproducibility between pathologists for the revised 2008 WHO diagnostic criteria to diagnose myeloproliferative disorders (MPD).

Eligibility criteria: Inclusion Criteria:

1. Patients with an elevated hemoglobin concentration (\>18 in males and \>16 in females) and who are suspected to have congenital or acquired primary polycythemia
2. Patients with a persistent thrombocytosis (\>400,000) that does not have an obvious secondary cause
3. Patients with a bone marrow biopsy that shows increased cellularity and fibrosis
4. Patients where there is clinical concern for primary myelofibrosis, such as anemia in combination with leukocytosis, thrombocytosis, splenomegaly and/or a leukoerythroblastic blood smear
5. Patients with thrombosis at unusual sites, such as Budd-Chiari syndrome, can have early PV before hemoglobin is elevated, these patients will also be included.

Exclusion Criteria:

1. Subjects who have a known acquired cause of polycythemia (increased hemoglobin/hematocrit) such as people living in high altitudes (in excess of 14,000 feet), subjects with heart disease, left to right heart shunt, severe hypoxia or severe pulmonary disease will be excluded from this study.
2. Subjects with a known acquired cause of thrombocytosis.
3. Subjects will be excluded if they cannot demonstrate decision making capacity sufficient to agree or decline the blood drawing or use of their blood for the study.

Primary outcomes:
measure: Identify genes whose mutations cause Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis.
timeFrame: Weekly
Secondary outcomes:
measure: To determine if there are proteins expressed by cells from patients that might be targets for the immune response.
timeFrame: Weekly
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Josef T Prchal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jelinek J, Li J, Mnjoyan Z, Issa JP, Prchal JT, Afshar-Kharghan V. Epigenetic control of PRV-1 expression on neutrophils. Exp Hematol. 2007 Nov;35(11):1677-83. doi: 10.1016/j.exphem.2007.09.008.
citation: Agarwal N, Mojica-Henshaw MP, Simmons ED, Hussey D, Ou CN, Prchal JT. Familial polycythemia caused by a novel mutation in the beta globin gene: essential role of P50 in evaluation of familial polycythemia. Int J Med Sci. 2007 Oct 4;4(4):232-6. doi: 10.7150/ijms.4.232.
citation: Gaikwad A, Verstovsek S, Yoon D, Chang KT, Manshouri T, Nussenzveig R, Cortes J, Vainchenker W, Prchal JT. Imatinib effect on growth and signal transduction in polycythemia vera. Exp Hematol. 2007 Jun;35(6):931-8. doi: 10.1016/j.exphem.2007.03.012.
citation: Chen GL, Prchal JT. X-linked clonality testing: interpretation and limitations. Blood. 2007 Sep 1;110(5):1411-9. doi: 10.1182/blood-2006-09-018655. Epub 2007 Apr 13.
citation: Gaikwad A, Nussenzveig R, Liu E, Gottshalk S, Chang K, Prchal JT. In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2 V617F allele. Exp Hematol. 2007 Apr;35(4):587-95. doi: 10.1016/j.exphem.2006.12.007.
citation: Hoffman R, Prchal JT, Samuelson S, Ciurea SO, Rondelli D. Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment. Biol Blood Marrow Transplant. 2007 Jan;13(1 Suppl 1):64-72. doi: 10.1016/j.bbmt.2006.11.003.
citation: Nussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S, Prchal JF, Prchal JT. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol. 2007 Jan;35(1):32-8. doi: 10.1016/j.exphem.2006.11.012.
citation: Chen GL, Liu E, Naidoo K, Popat U, Coetzer TL, Prchal JT. Idiopathic myelofibrosis without dacryocytes. Haematologica. 2006 Jun;91(6 Suppl):ECR29.
citation: Finazzi G, Gregg XT, Barbui T, Prchal JT. Idiopathic erythrocytosis and other non-clonal polycythemias. Best Pract Res Clin Haematol. 2006;19(3):471-82. doi: 10.1016/j.beha.2005.07.006.
citation: Chen G, Prchal JT. Polycythemia vera and its molecular basis: an update. Best Pract Res Clin Haematol. 2006;19(3):387-97. doi: 10.1016/j.beha.2005.07.003.
citation: Popat U, Frost A, Liu E, Guan Y, Durette A, Reddy V, Prchal JT. High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2 mutation differentiate myelofibrosis with myeloid metaplasia from secondary myelofibrosis associated with pulmonary hypertension. Blood. 2006 May 1;107(9):3486-8. doi: 10.1182/blood-2005-08-3319. Epub 2006 Jan 17.
citation: Skoda R, Prchal JT. Chronic myeloproliferative disorders--introduction. Semin Hematol. 2005 Oct;42(4):181-3. doi: 10.1053/j.seminhematol.2005.08.004. No abstract available.