Blood and Lymph Conditions

All Conditions

Neoplasms

Rare Diseases

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Bone Marrow Diseases

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antisickling Agents

All Drugs and Chemicals

Hydroxyurea

All patients will receive ruxolitinib at a starting dose of 10 mg twice daily which could be titrated to most appropriate dose. Dose was not to exceed 25 mg bid nor be less than 5 mg once a day

supplied as 5 mg, 10 mg and 20 mg tablets to be taken orally

Ruxolitinib

Novartis Pharmaceuticals

The purpose of this open-label, single arm, multi-center Expanded Treatment Protocol (ETP) was to provide early access to ruxolitinib and evaluate safety information in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and who had no other standard treatment option, nor did they qualify for another clinical study for PV

Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.

An Open-label, Multi-center, Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Are Available.

Change in hematocrit levels from Baseline to each visit were measured

Change in spleen length from Baseline to each visit

The MPN-SAF (Appendix 6) was a disease specific questionnaire comprised of 10 items that measures fatigue related to MPN disease and the severity of nine of the most prevalent associated symptoms including: early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain, fever and weight loss. There were three recall periods used in this questionnaire, which were 24 hours for fatigue, the past week for symptoms of early satiety, abdominal discomfort, inactivity, concentration, night sweats, itching, bone pain and fever, and the past 6 months for weight loss, Each item was scored on a scale ranging from 0 (no fatigue/absent) to 10 (As bad as you can imagine/worst imaginable). The MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale.

The MPN-SAF TSS thus had a possible score range of 0 to 100.

All Patients

<= 60

Age, Customized

Sex: Female, Male

Caucasian

Asian

Other

Race/Ethnicity, Customized

Resistant to hydroxyurea

Intolerant to hydroxyurea

Definition of resistant or intolerant was based on physician's evaluation

Number of participants resistant or intolerant to hydroxyurea (HU)

1 phlebotomy

2 phlebotomies

>=3 phlebotomies

Missing

Number of participants' frequency of phlebotomy in 52 weeks prior to screening

Prior Hydroxyurea use

Prior other anti-neoplastic medications use

Other prior anti-neoplastic medications included busulfan, interferon, peginterferon, pipobroman, anagrelide, momelotinib, tioguanine, mercapturine and sodium phosphate

Number of participants' use of prior antineoplastic therapy

Study Director

Adverse events

Serious adverse events

Number of Participants With Adverse Events - All Grades

Week 4

Week 8

Week 12

Week 16

Week 20

Week 24

Week 36

Week 48

Week 60

Week 72

Week 84

Week 96

Baseline

Post-baseline

Change

Number of participants qualifying for evaluation of change from baseline varied across visits

Change From Baseline in Hematocrit Levels at All Visits

End of treatment

Change From Baseline in Spleen Length

Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

Overall Study

Heart and Blood Diseases

Thrombosis

Venous Thrombosis

Thrombocytosis

Thrombocythemia, Essential

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Anti-Infective Agents

Aspirin

Interferons

Interferon-alpha

Peginterferon alfa-2a

Interferon alpha-2

Antiviral Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Immunologic Factors

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.

PEGASYS

John Mascarenhas, MD

Ellen Ritchie, MD

Alessandro Rambaldi, MD

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.

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.

Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)

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

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

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

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Were Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Was Available.	NCT02292446	Polycythemia Ve...	Ruxolitinib	18 Years -	Novartis
Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or Essential Thrombocythemia (ET)	NCT01259817	High Risk Polyc... High Risk Essen...	PEGASYS Aspirin	18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for hydroxyurea resistant