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Report for Clinical Trial NCT01259817

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyurea Resistant or Intolerant or Have Had Abdominal Vein Thrombosis

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.

NCT01259817 High Risk Polycythemia Vera High Risk Essential Thrombocythemia
MeSH:Polycythemia Vera Polycythemia Thrombocytosis Thrombocythemia, Essential
HPO:Polycythemia Thrombocytosis

2 Interventions


Description: Patient will start at 45 micrograms per week and gradually increase to 180 micrograms per week. Pegasys will be supplied in prefilled syringes and are to be given subcutaneously.
Type: Drug
Group Labels: 1


Name: Aspirin

Description: 81 or 100 mg daily.
Type: Drug
Group Labels: 1


Primary Outcomes

Measure: 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: 4 years

Secondary Outcomes

Measure: 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: 4 years

Measure: To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden.

Time: 4 years

Description: Improvement in disease symptoms will be measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study.

Measure: 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: 4 years

Description: We plan to capture the rate of disease progression to a more advanced myeloid malignancy.

Measure: To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation during therapy Pegylated Interferon Alfa-2a.

Time: 4 years

Description: Capture and record the cardiovascular events that occur during the study.

Measure: Estimate the observed incidence of major cardiovascular events during therapy Pegylated Interferon Alfa-2a.

Time: 4 years

Description: 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.

Measure: 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: 4 years

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment

There is one SNP


1 V617F

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.. --- V617F ---

For these patients the following additional inclusion/exclusion criteria apply: - > 3 months since onset of SVT - SVT treated with oral anticoagulants but no aspirin - Liver enzymes not > 2 times the normal value - Absence of encephalopathy, refractory or infected ascites, esophageal varicose of grade > 1 at time of trial entry - Bone marrow biopsy confirmed diagnosis of PV or ET - JAK2-V617F mutations present - These patients may have a normal blood count at trial entry - Age over 18 years (no upper age limit) - Able and willing to comply with study criteria - Signed and informed consent to participant in this study - Willing to participate in associated correlative science biomarker study - Serum creatinine < 1.5 x upper limit of normal - AST and ALT < 2 x upper limit of normal - Total bilirubin within normal limits Exclusion Criteria: - Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). --- V617F ---

The point mutation in JAK2 encodes a valine to phenylalanine change at position 617 (JAK2 V617F), and confers constitutive tyrosine kinase activity. --- V617F ---

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. --- V617F ---

It is estimated that 95% of PV cases carry JAK2 V617F, while 50 to 60% of ET and PMF cases are JAK2 V617F+. --- V617F ---

HPO Nodes