Clinical Trial: Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyure
Brief Summary:
The aim of this research is to look at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increases the risk of developing blood clots.
It is important for patients with ET or PV who are at risk of blood clots to receive drugs which will minimize the risks of developing these blood clots but at the moment the investigators are not sure which drugs will best control the disorder.
The purpose of this study is to look at the effectiveness of giving patients who have been diagnosed with ET and PV a study drug regimen using Aspirin and PEGASYS (also known as Pegylated interferon alfa-2a, instead of the standard treatment drug called Hydroxyurea (or hydroxycarbamide or Hydroxyurea), for whom this drug may not be suitable. The drug may not be suitable either because it is not adequately controlling the number of blood cells or some specific side effects occur.
Detailed Summary:
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 gr
Sponsor: Ronald Hoffman
Current Primary Outcome: Evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response in patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchnic vein thrombosis [ Time Frame: 4 years ]
Original Primary Outcome: Evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response in patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchic vein thrombosis [ Time Frame: 4 years ]
Current Secondary Outcome:
- To evaluate the toxicity and tolerability of therapy Pegylated Interferon Alfa-2a in each of the 3 strata by recording the number of adverse events that occur during the study by using CTC 4.0 as the guide. [ Time Frame: 4 years ]
- To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden. [ Time Frame: 4 years ]
- To evaluate specific pre-defined toxicity and tolerance of Pegylated Interferon Alfa-2a through a sequential structured symptom assessment package of patient reported outcome instruments. [ Time Frame: 4 years ]Improvement in disease symptoms will be measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study.
- To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation during therapy Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]We plan to capture the rate of disease progression to a more advanced myeloid malignancy.
- Estimate the observed incidence of major cardiovascular events during therapy Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]Capture and record the cardiovascular events that occur during the study.
- To measure the impact of Pegylated Interferon Alfa-2a on JAK2-V617F, CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities. [ Time Frame: 4 years ]The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.
Original Secondary Outcome:
- To evaluate the toxicity and tolerability of therapy Pegylated Interferon Alfa-2a in each of the 3 strata by recording the number of adverse events that occur during the study by using CTC 4.0 as the guide. [ Time Frame: 4 years ]
- To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden. [ Time Frame: 4 years ]
- To evaluate specific pre-defined toxicity and tolerance of Pegylated Interferon Alfa-2a through a sequential structured symptom assessment package of patient reported outcome instruments. [ Time Frame: 4 years ]Improvement in disease symptoms will be measured by the MP instrument being used in this study.
- To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]We plan to capture the rate of disease progression to a more advanced myeloid malignancy.
- Estimate the observed incidence of major cardiovascular events after therapy Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]Capture and record the cardiovascular events that occur during the study.
- To measure the impact of Pegylated Interferon Alfa-2a on JAK2-V617F, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities. [ Time Frame: 4 years ]The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abormalities will be measured by seeing if the cytogenetics go from abnormal to normal.
Information By: Icahn School of Medicine at Mount Sinai
Dates:
Date Received: December 6, 2010
Date Started: September 2011
Date Completion:
Last Updated: January 10, 2017
Last Verified: January 2017
