7 studies in Myeloproliferative Disorders
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Multiple Ascending Dose of BMS-911543
Rochester, MN
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Multiple Ascending Dose of BMS-911543
Location:
Rochester, MNTrial status:
Open for EnrollmentWhy is this study being done?
The purpose of this first in human study is to determine if BMS-911543 is safe and tolerable in subjects with symptomatic intermediate-1, intermediate-2 or high risk myelofibrosis to permit clinical testing at the Maximum Tolerated Dose or at a Clinically Active Dose, and to determine if BMS-911543 will demonstrate efficacy in symptomatic myelofibrosis.
NCT ID:
NCT01236352IRB Number:
11-000950Who can I contact for additional information about this study?
Rochester: Animesh D. Pardanani, Site 004
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Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF
Scottsdale and Phoenix, AZ
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Safety and Tolerability Study of Oral NS-018 in Patients With Primary Myelofibrosis (MF), Post-polycythemia Vera MF or Post-essential Thrombocythemia MF
Location:
Scottsdale and Phoenix, AZTrial status:
Open for EnrollmentWhy is this study being done?
The purpose of this study is to determine the safety and tolerability of orally administered NS-018 in patients with Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (post-ET MF)
NCT ID:
NCT01423851IRB Number:
11-000895Who can I contact for additional information about this study?
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Scottsdale: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
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Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET)
Scottsdale and Phoenix, AZ
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Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET)
Location:
Scottsdale and Phoenix, AZTrial status:
Open for EnrollmentWhy is this study being done?
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are a group of clonal hematological malignancies that are characterized by a chronic course which can be punctuated by a number of disease related events including thrombosis, hemorrhage, pruritis and leukemic transformation. These disorders include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PM). Recently an acquired somatic mutation in the intracellular kinase, JAK2 (JAK2V617F) has been observed in 95% of patients with PV, 50% of patients with ET and 50% of patients with primary myelofibrosis. At present the chemotherapeutic agent hydroxyurea is the standard of care for high risk patients with PV. Concern exists about prolonged use of this drug leading to leukemia and the inability of hydroxyurea to eliminate the malignant clone. Interferon (rIFN -2b), is a drug that appears to be non-leukemogenic, and may have a preferential activity on the malignant clone in PV, as suggested by cytogenetic remissions obtained in patients treated with rIFN -2b. Several investigators recently reported that patients with PV treated with rIFN -2b had lower JAK2V617F allele burdens as compared to a control group that included patients treated with phlebotomy, hydroxyurea, or anagrelide, or who remained untreated. The results confirm the hypothesis that rIFN -2b preferentially targets the malignant clone in PV and raises the possibility that the JAK2V617F allele burden, and a reversion of clonal hematopoiesis monitored in females by expression of X-chromosome polymorphic alleles maybe useful in monitoring minimal residual disease in PV patients. Pegylated Interferon Alfa-2a (PEGASYS) has been demonstrated in phase II trials of patients with PV and ET to have clinical efficacy as measured by normalization of myeloproliferation, lack of vascular events while on therapy, and a decrease in the JAK2V617F allele burden. Overall the tolerability of the therapy was good, with each of these trials having a dropout rate secondary to toxicity of less than 10% of those enrolled. Although dropout rates for toxicity were low, that is not to say the therapy was without symptomatic toxicity, and indeed a spectrum of toxicities might be encountered and need to be weighed in the analysis of the net clinical benefit patients experience on a clinical trial with Pegylated Interferon Alfa-2a. A new MPN assessment form will be utilized in this study. This 19 item instrument includes a previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. The instrument yields an independent result for each symptom (fatigue is a composite score), as this methodology (of linear analog scale assessment [LASA]) has proven very valid in the past. This instrument was validated prospectively (by comparison to a panel of instruments each containing an aspect of the MPN-SAF) for administration at a single time point. This is a randomized trial between hydroxyurea and Pegylated Interferon Alfa-2a, it is an open label clinical trial in two independent disease strata: (1) high risk polycythemia vera and (2) high risk essential thrombocythemia.
NCT ID:
NCT01259856IRB Number:
11-006934Who can I contact for additional information about this study?
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Scottsdale: Ruben Mesa, MD 480-301-8335
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Imetelstat Sodium in Treating Patients With Primary or Secondary Myelofibrosis
Rochester, MN
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Imetelstat Sodium in Treating Patients With Primary or Secondary Myelofibrosis
Location:
Rochester, MNTrial status:
Open for EnrollmentWhy is this study being done?
PRIMARY OBJECTIVES: I. To evaluate overall response rate. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis (MF) (per common terminology criteria for adverse events, version 4.03). II. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by physical examination (palpable distance from the left costal margin). III. To evaluate the efficacy of imetelstat in inducing red blood cell transfusion-independence in previously transfusion-dependent patients (per International Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria). TERTIARY OBJECTIVES: I. To evaluate the effect of imetelstat on bone marrow histology and karyotype. II. To evaluate the effect of imetelstat on leukocytosis and thrombocytosis. OUTLINE: Patients receive imetelstat sodium intravenously (IV) over 2 hours on day 1. Treatment repeats every 21 days for up to 52 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 5 years.
NCT ID:
NCT01731951IRB Number:
12-005104Who can I contact for additional information about this study?
Rochester: Mayo Clinic Clinical Trials Referral Office 507-538-7623
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Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)
Scottsdale and Phoenix, AZ
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Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)
Location:
Scottsdale and Phoenix, AZTrial status:
Open for EnrollmentWhy is this study being done?
Myeloproliferative disorders (MPDs) are clonal hematologic diseases characterized by the excess production of one or more lineages of mature blood cells, a predisposition to bleeding and thrombotic complications, extramedullary hematopoiesis, and a variable progression to acute leukemia. The classical Philadelphia chromosome-negative MPDs are polycythemia vera (PV), characterized by an expansion in red blood cell production; essential thrombocythemia (ET), characterized by an isolated elevation in the platelet count; and myelofibrosis, distinguished by a fibrotic bone marrow and peripheral blood cytopenias, and accompanied by the highest risk of leukemic transformation. Myelofibrosis can arise de novo, as primary myelofibrosis (PMF), or can evolve out of PV or ET as those diseases progress (so called post-PV MF and post-ET MF). Amongst the MPDs, those characterized by myelofibrosis (PMF together with post-PV and post-ET MF) carry the worst prognosis, with a median survival on the order of 3 to 5 years. Patients typically present with anemia, often requiring transfusions, symptomatic splenomegaly and severe constitutional symptoms. Donor stem cell transplantation is the only potentially curative therapy. To date there is no therapy for myelofibrosis that has been shown to offer a survival benefit, and all other therapies for myelofibrosis are palliative. In 2005, a major breakthrough in understanding the pathophysiology of MPDs came when 4 groups described a recurrent somatic mutation in Janus kinase 2 (JAK2) in the majority of patients with MPDs. The point mutation in JAK2 encodes a valine to phenylalanine change at position 617 (JAK2 V617F), and confers constitutive tyrosine kinase activity. Introducing the mutation into the bone marrow of mouse models recapitulates the PV phenotype (complete with evolution to bone marrow fibrosis) and inhibitors of JAK2 attenuate the growth of cell lines bearing the mutation in vitro and in vivo, suggesting that JAK2 V617F is a pathophysiologically relevant therapeutic target. It is estimated that 95% of PV cases carry JAK2 V617F, while 50 to 60% of ET and PMF cases are JAK2 V617F+. The discovery of the JAK2V617F mutation in nearly all patients with PV and half those with ET and PMF have redefined the classification and possibly the management of MPNs. Despite the discovery of the JAK2V617F mutation, many of the clinical questions in the management of MPNs remain unanswered. In PV, for example, cardiovascular mortality remains 1.4 to 1.6 times that of the reference normal population with leukemia and myelofibrosis rates many times increased over baseline. Debate continues over the role of venesection versus cytoreduction as first-line therapy, and whether hydroxycarbamide (Hydroxyurea) is associated with better thrombotic prophylaxis and/or a higher rate of leukemic transformation. Interferons may produce molecular responses in PV patients. In high-risk ET, while Hydroxyurea and aspirin appear to be more optimal than anagrelide and aspirin, vascular complications remain the most significant cause of mortality and morbidity, suggesting that targeting vascular risk factors may be worthwhile. Furthermore while Hydroxyurea is regarded as the first-choice therapy in most of high risk patients with ET and PV; up to 10% of the patients do not attain the desired reduction of platelet number or hematocrit with the recommended dose of the drug, exhibiting clinical resistance, whereas some will develop unacceptable side effects, demonstrating clinical intolerance. Quantitation of the JAK2V617F allele burden provides for the first time the opportunity to monitor the effect of potential therapeutic agents on the malignant clone in patients with PV. Great enthusiasm has been expressed for the use of small molecule inhibitors of JAK2 for the treatment of patients with MPN. Phase 1/2 trials have indicated greater than expected toxicity, non specificity of action and an inability of these compounds to dramatically alter the JAK2V617F allele burden. Interferon (rIFN -2b), is a drug that appears to be non-leukemogenic (contrary to 32P, alkylating agents, and possibly Hydroxyurea), and may have a preferential activity on the malignant clone in PV, as suggested by cytogenetic remissions obtained in patients treated with rIFN -2b. This trial was designed as open-label phase 2 study conducted in two strata of patients with high risk PV or ET who were intolerant of hydroxyurea. Patients with ET or PV with Splanchnic Vein Thrombosis (regardless of prior hydroxyurea) are enrolled in separate strata.
NCT ID:
NCT01259817IRB Number:
12-002751Who can I contact for additional information about this study?
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Scottsdale: Ruben A Mesa, MD 480-301-8335
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Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis
Scottsdale and Phoenix, AZ
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Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis
Location:
Scottsdale and Phoenix, AZTrial status:
Open for EnrollmentWhy is this study being done?
PRIMARY OBJECTIVES: I. To evaluate the efficacy (best overall response) of ruxolitinib (ruxolitinib phosphate) and danazol in patients with myelofibrosis suffering from anemia. SECONDARY OBJECTIVES: I. To evaluate the overall survival of patients with myelofibrosis suffering from anemia initiating ruxolitinib and danazol. II. To evaluate the adverse event profile of ruxolitinib and danazol in patients with myelofibrosis suffering from anemia. TERTIARY OBJECTIVES: I. To evaluate quality of life (QOL) and patient-reported symptoms using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) with ruxolitinib and danazol for patients with myelofibrosis suffering from anemia. OUTLINE: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) and danazol PO thrice daily (TID) on days 1-56. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
NCT ID:
NCT01732445IRB Number:
12-002466Who can I contact for additional information about this study?
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Scottsdale: Mayo Clinic Clinical Trials Referral Office 507-538-7623
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Correlative Biomarker Study in Patients With Myeloproliferative Disorders
Scottsdale and Phoenix, AZ
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Correlative Biomarker Study in Patients With Myeloproliferative Disorders
Location:
Scottsdale and Phoenix, AZTrial status:
Open for EnrollmentWhy is this study being done?
Researchers will use abnormal blood and/or bone marrow cells, or materials derived from these abnormal cells, like DNA, RNA, protein or plasma, in laboratory studies. Toenail clippings will provide normal material like DNA for comparison with the abnormal material derived from the blood and/or bone marrow. The results of these studies will be correlated with subjects' disease symptoms and response to their experimental treatment. The MPD-RC researchers are interested in studying molecules from the blood and bone marrow, the exact molecules changing over time with the investigators choosing only the most promising for investigation. The investigators are attempting to better understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases. These syndromes carry a high risk of developing leukemia. It is important to continue to learn more about these blood cancers and to learn more about the effectiveness and potential side effects of various treatments. It is believed that further basic knowledge about these cancer cells as well as the effects of treatment will lead to the improvement of current therapies and the development of entirely new treatments for these diseases. The MPD-RC is hoping to determine if a number of laboratory tests (biomarkers) will allow for the prediction of response in future patients to the treatment they would receive.
NCT ID:
NCT00665067Who can I contact for additional information about this study?
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Scottsdale: Ruben Mesa, MD 480-301-8335
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