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

A Prospective, Multicenter, Randomized Controlled Clinical Trial of Pegylated Interferon Alfa-2b Versus Interferon Alfa Therapy in the Treatment of Adult Essential Thrombocythemia

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.

Study Overview

• Status: Recruiting
• Conditions: Essential Thrombocytopenia
• Intervention / Treatment: Drug: Recombinant Interferon Alpha; Drug: Pegylated interferon alfa-2b

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.

• Study Type: Interventional
• Enrollment (Estimated): 194
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lei Zhang, MD; Phone Number: 8602223909240; Email: zhanglei1@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Recombinant Interferon Alpha; 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; 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.
Experimental: Pegylated Interferon Alfa-2b; 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; 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.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of immune cell subgroups	The proportion of T lymphocyte, B lymphocyte and dendritic cell subsets and the changes of gene expression profile of these cells will be analyzed before and after treatment.	From the start of study treatment (Week 0) up to the end of Week 52.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Lei Zhang, MD, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Interferon Alfa; Pegylated Interferon Alfa-2b; Essential Thrombocytopenia
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombocytosis; Thrombocythemia, Essential; Thrombocytopenia; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: Peg-IFNα-ET-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No