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

Phase 2
Recruiting
Conditions
Essential Thrombocytopenia
Interventions
Drug: Recombinant Interferon Alpha
Drug: Pegylated interferon alfa-2b
Registration Number
NCT05395507
Lead Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
194
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Recombinant Interferon AlphaRecombinant Interferon AlphaRecombinant 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.
Pegylated Interferon Alfa-2bPegylated interferon alfa-2bPegylated 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.
Primary Outcome Measures
NameTimeMethod
Complete hematological remission (CHR) ratesFrom the start of study treatment (Week 0) up to the end of Week 52

The CHR rates defined as European Leukemia Net will be compared between the two groups.

Secondary Outcome Measures
NameTimeMethod
Impact of therapy on non-driver mutationsFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the proportion of subjects that display change on key non-driver biomarkers of the disease-DNMT3A, ASXL1, TET2 or other mutations.

The incidence of progressing to bone marrow fibrosisFrom the start of study treatment (Week 0) up to the end of Week 52.

The incidence of progressing to bone marrow fibrosis will be compared between the two groups

CHR rates at week 24 and 36From the start of study treatment (Week 0) up to the end of Week 24 and Week 36, respectively

The CHR rates at week 24 and 36 will be compared between the two groups

Time to CHRFrom the start of study treatment (Week 0) up to the end of Week 52.

The time of reaching CHR will be compared between the two groups

Change of bone marrow pathologyFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the rate of patients with improvement and no progress rate of bone marrow pathology between the two groups

The incidence of major bleeding eventsFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the incidence of major bleeding events between the two groups.

The proportion of patients crossed to the contralateral groupFrom the start of study treatment (Week 0) up to the end of Week 52.

The proportion of patients crossed to the contralateral group will be compared between the two groups

The CHR rates after crossoverFrom the start of study treatment (Week 0) up to the end of Week 52.

The CHR rates within 52 weeks after crossover

Change of splenomegalyFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the proportion of subject with improvement and no progress rate of splenomegaly between the two groups.

The incidence of major thrombotic eventsFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the incidence of major thrombotic events between the two groups.

Impact of therapy on driver mutationsFrom the start of study treatment (Week 0) up to the end of Week 52.

To compare the proportion of subjects that display change on key biomarkers of the disease- JAK2V617F, CALR, MPL mutations.

The incidence of progressing to acute leukemiaFrom the start of study treatment (Week 0) up to the end of Week 52.

The incidence of progressing to acute leukemia will be compared between the two groups

Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom scoreFrom the start of study treatment (Week 0) up to the end of Week 52.

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.

Change of quality of lifeFrom the start of study treatment (Week 0) up to the end of Week 52.

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).

Change of microcirculation disturbanceFrom the start of study treatment (Week 0) up to the end of Week 52.

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

Specific pre-defined toxicityFrom the start of study treatment (Week 0) up to the end of Week 52.

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.

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital

🇨🇳

Tianjin, Tianjin, China

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