Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in Adult Essential Thrombocythemia

Study Overview
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Brief Summary
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Objectives: To compare the efficacy and safety in Adult patients (≥18 years) diagnosed as essential thrombocythemia treated with the Pegylated Interferon Alfa-2b vs. Interferon Alfa. Study Design: A prospective, open-label, multicenter, randomized controlled clinical trial.

Detailed Description
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This is a prospective, open-label, multicenter, randomized controlled clinical trial between Interferon Alfa and Pegylated Interferon Alfa-2b in adult essential thrombocythemia (≥18 years). Patients will be randomly divided into the following two treatment groups: 1. Recombinant Interferon Alpha, with an initial dose of 300 wu three times a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available. 2. Pegylated Interferon Alfa-2b, with an initial dose of 135 ug at week 0 , and then 180 ug once a week from week 1 to week 52. 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
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A Prospective, Multicenter, Randomized Controlled Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Adult Essential Thrombocythemia

Conditions
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Essential Thrombocytopenia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old. Male or Female. Diagnosis of essential thrombocythemia according to the 2016 World Health Organization criteria. Those who have not use interferon within 4 weeks before the first medication. Patients with indications for cytoreductive therapy. Men and women with reproductive potential, as well as all women with menopause less than 2 years, must agree to use acceptable contraceptive methods until 28 days after the last dose of study drug, and women must agree not to breastfeed during the study period. Voluntary written informed consent. Exclusion Criteria: Resistance, or intolerance, or any contraindications to interferon. Patients with active thrombosis or active bleeding. Neutrophil count < 1.0x10^9/L. Hemoglobin < 11g/dL for male, or < 10g/dL for female. 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 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: 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 three times a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available. | Drug: Recombinant Interferon Alpha<br>* Recombinant Interferon Alpha, with an initial dose of 300 wu three times a week. Other interferons that have been listed can be used if Recombinant Interferon Alpha (300 wu) is not available.<br>|
| Experimental: Pegylated Interferon Alfa-2b<br>Pegylated Interferon Alfa-2b, with an initial dose of 135 ug at week 0 , and then 180 ug once a week from week 1 to week 52. | Drug: Pegylated interferon alfa-2b<br>* Pegylated Interferon Alfa-2b, with an initial dose of 135 ug at week 0 , and then 180 ug once a week from week 1 to week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete hematological remission (CHR) rates | The CHR rates defined as European Leukemia Net will be compared between the two groups. | From the start of study treatment (Week 0) up to the end of Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CHR rates at week 24 and 36 | The CHR rates at week 24 and 36 will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 24 and Week 36, respectively | 
| Time to CHR | The time of reaching CHR will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The proportion of patients crossed to the contralateral group | The proportion of patients crossed to the contralateral group will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The CHR rates after crossover | The CHR rates within 52 weeks after crossover | From the start of study treatment (Week 0) up to the end of Week 52. | 
| Impact of therapy on driver mutations | 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 (Week 0) up to the end of Week 52. | 
| Impact of therapy on non-driver mutations | To compare the proportion of subjects that display change on key non-driver biomarkers of the disease-DNMT3A, ASXL1, TET2 or other mutations. | From the start of study treatment (Week 0) up to the end of Week 52. | 
| Change of splenomegaly | To compare the proportion of subject with improvement and no progress rate of splenomegaly between the two groups. | From the start of study treatment (Week 0) up to the end of Week 52. | 
| Change of bone marrow pathology | To compare the rate of patients with improvement and no progress rate of bone marrow pathology between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The incidence of major thrombotic events | To compare the incidence of major thrombotic events between the two groups. | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The incidence of major bleeding events | To compare the incidence of major bleeding events between the two groups. | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The incidence of progressing to bone marrow fibrosis | The incidence of progressing to bone marrow fibrosis will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| The incidence of progressing to acute leukemia | The incidence of progressing to acute leukemia will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| 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. | From the start of study treatment (Week 0) up to the end of Week 52. | 
| Change of quality of life | Compare the rate of patients with improvement in quality of life between the two groups (assessed by EORTC quality of life scale QLQ-C30 V3.0 questionnaire). | From the start of study treatment (Week 0) up to the end of Week 52. | 
| Change of microcirculation disturbance | The rate of patients with improvement in microcirculation disturbance (such as pruritus, headache, dizziness, chest tightness, erythematous limb pain and limb paresthesia) will be compared between the two groups | From the start of study treatment (Week 0) up to the end of Week 52. | 
| 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 (Week 0) up to the end of Week 52. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential Thrombocytopenia, Interferon Alfa, Pegylated Interferon Alfa-2b, Efficacy, Safety