High Risk Essential Thrombocythemia Clinical Trial
Official title:
Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET)
This research is looking 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.
The purpose of this study is to look at the effectiveness of giving participants who have
been diagnosed with ET or PV one of two different study regimens over time. The study subject
will be followed for their condition for about 5 years. The subject will be randomized into
one of two study regimens, either Pegylated Interferon Alfa-2a (PEGASYS) or Aspirin and
Hydroxyurea (also called Hydroxycarbamide). The subject must be newly diagnosed or already
receiving treatment for either PV or ET. Each of the study drugs used in this study is
already being used to treat subjects with ET or PV currently, but the investigators are
unsure which study drug is better.
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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01259817 -
Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)
|
Phase 2 |