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

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

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

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, 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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lei Zhang, MD; Phone Number: +862223909240; Email: zhanglei1@ihcams.ac.cn
• Study Contact Backup: Name: Rongfeng Fu, MD; Phone Number: +862223909009; Email: furongfeng@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Lei Zhang, MD; Phone Number: +862223909240; Email: zhanglei1@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-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 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; 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;
Experimental: Pegylated Interferon Alfa-2b; 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; 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).

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

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): January 10, 2020
• Primary Completion (Estimated): February 20, 2024
• Study Completion (Estimated): February 20, 2024

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Adolescent; Essential Thrombocythemia; Childhood; Interferon Alfa; Pegylated Interferon Alfa-2b
• 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: IHBDH-IIT2019001

Drug and device information, study documents

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