Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in Childhood and Adolescent Essential Thrombocythemia

Study Overview
=================
Brief Summary
-----------------
Objectives: To compare the efficacy and safety in childhood and adolescent patients (<20 years) diagnosed as essential thrombocythemia treated with the Pegylated Interferon Alfa-2b vs. Interferon Alfa. Study Design: A prospective, open-label, nonrandomized, single-center clinical trial

Detailed Description
-----------------
This is a prospective, open-label, nonrandomized, single-center clinical trial between Interferon Alfa and Pegylated Interferon Alfa-2b in childhood and adolescent essential thrombocythemia (<20 years). Patients will be divided into the following two treatment groups: 1. Recombinant Interferon Alpha, with an initial dose of 300 wu twice a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available, and the specific dose will be determined by the researchers; 2. Pegylated Interferon Alfa-2b, with an initial dose of 135 ug once a week (body surface area < 1.73 m2) or 180 ug once a week ( body surface area≥1.73 m2). The current drug therapies and possible risks of Pegylated Interferon Alfa-2b and Interferon Alfa in the treatment of childhood and adolescent essential thrombocythemia will be fully introduced to the guardians (childhood patients) or patients (adolescent patients) by the researchers. Then the patients will be divided into one of the two groups according to the guardians' (childhood patients) or patients' (adolescent patients) will. The dosage will be adjusted according to the results of laboratory examinations and patient tolerance. The patient will be transferred to the other group if intolerance or resistance occurs.

Official Title
-----------------
A Prospective, Single-center Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Childhood and Adolescent Essential Thrombocythemia

Conditions
-----------------
Essential Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Recombinant Interferon Alpha
* Drug: Pegylated interferon alfa-2b


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: <20 years old Male or Female Diagnosis of essential thrombocythemia according to the 2016 WHO criteria. Platelet count ≥ 450 × 109 / L for more than 6 months（If the patient has JAK2 V617F, CALR or MPL gene mutation, the history may be less than 6 months） Platelet count ≥ 1000 × 109 / L or other therapeutic indications at screening. The guardians has provided written informed consent prior to enrollment Exclusion Criteria: Known to meet the criteria for primary myelofibrosis or polycythemia vera by 2016 WHO criteria Presence of any life-threatening co-morbidity Secondary thrombocytosis Familial thrombocytosis Resistance, or intolerance, or any contraindications to interferon Interferon is used in the past 1 month before enrollment Patients with previous or present thrombosis or active bleeding WBC<4× 109 / L HGB<110g/L Poor control of thyroid dysfunction Patients with a prior malignancy within the last 3 years Patients with severe cardiac or pulmonary dysfunction Severe renal damage (creatinine clearance < 30 ml / min) Severe liver dysfunction (ALT or AST > 2.5×ULN) Patients diagnosed as diabetes with poor control Patients with hepatitis B virus, hepatitis C virus replication or HIV infection Patients with a history of drug / alcohol abuse (within 2 years before the study) Patients that have participated in other experimental researches within one month before enrollment History of psychiatric disorder Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial

Ages Eligible for Study
-----------------
Maximum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Recombinant Interferon Alpha<br>Recombinant Interferon Alpha, with an initial dose of 300 wu twice a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available, and the specific dose will be determined by the researchers. | Drug: Recombinant Interferon Alpha<br>* Recombinant Interferon Alpha, with an initial dose of 300 wu twice a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available, and the specific dose will be determined by the researchers;<br>|
| Experimental: Pegylated Interferon Alfa-2b<br>Pegylated Interferon Alfa-2b, with an initial dose of 135 ug once a week (body surface area < 1.73 m2) or 180 ug once a week ( body surface area≥1.73 m2). | Drug: Pegylated interferon alfa-2b<br>* Pegylated Interferon Alfa-2b, with an initial dose of 135 ug once a week (body surface area < 1.73 m2) or 180 ug once a week ( body surface area≥1.73 m2).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in platelet count | Proportion of subjects with a continuous platelet count ≤600×109/L or decrease ≥50% (<1000×109/L ) from baseline during treatment will be evaluated. | From the start of study treatment (Day 1) up to the end of month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The complete hematologic response rates | To compare the complete hematologic response rates between different treatment groups | From the start of study treatment (Day 1) up to the end of month 12 | 
| Time to response in platelet count | Time to response in platelet count (<600×109/L) between different treatment groups | From the start of study treatment (Day 1) up to the end of month 12 | 
| Impact of therapy on key biomarkers | To compare the proportion of subjects that display change on key biomarkers of the disease- JAK2V617F, CALR, MPL mutations. | From the start of study treatment (Day 1) up to the end of month 12 | 
| Incidence of major cardiovascular and thrombotic events | To estimate incidence of major cardiovascular and thrombotic events (defined as cardiovascular death, myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, Budd Chiari syndrome, deep vein thrombosis, and any other clinically relevant thrombotic event) while on active treatment or observation following end of treatment between different treatment groups | From the start of study treatment (Day 1) up to the end of month 12 | 
| Incidence of development of myelodysplastic disorders, myelofibrosis, or leukemic transformation. | To estimate incidence of development of myelodysplastic disorders, myelofibrosis, or leukemic transformation between different treatment groups | From the start of study treatment (Day 1) up to the end of month 12 | 
| Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score | To compare the proportion of subjects that display change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (0-100 scores, higher scores mean a worse outcome) between different treatment groups. | 12 months | 
| Specific pre-defined toxicity | To compare incidence of specific pre-defined toxicity including fatigue, flu-like symptoms, dizziness, injection site necrosis, dyspnea, pain, depression, blurred Vision, insomnia, anorexia, weight Loss, weakness, pruritis, sweating, fever, decreased Libido, hot Flashes, flushing. | From the start of study treatment (Day 1) up to the end of month 12 | 
| Impact of therapy on bone marrow histopathology | To compare the proportion of subjects that display change on bone marrow histopathology | From the start of study treatment (Day 1) up to the end of month 12 | 
| Impact of therapy on cytogenetic abnormalities | To compare the proportion of subjects that display change on cytogenetic abnormalities. | From the start of study treatment (Day 1) up to the end of month 12 | 
| Death while on active treatment or observation following end of treatment | To compare the incidence of death while on active treatment or observation following end of treatment | From the start of study treatment (Day 1) up to the end of month 12 | 
| Change in platelet count | Proportion of subjects with a continuous platelet count <1000×109/L during treatment will be evaluated. | From the start of study treatment (Day 1) up to the end of month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Essential Thrombocythemia, Childhood, Interferon Alfa, Pegylated Interferon Alfa-2b, Adolescent