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Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV (PV)

Primary Purpose

Polycythemia Vera

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Ruxolitinib
Pegylated interferon α-2b
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycythemia Vera

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ≥18 years old. Male or Female. Meets the diagnostic criteria for Polycythemia Vera according to WHO-2022. Resistant or intolerant to hydroxyurea (based on the 2013 European LeukemiaNet criteria). Have not previously received interferon preparations or ruxolitinib treatment, or the washout period between the last use of interferon preparations or ruxolitinib and the first use of the study drug should not be less than 4 weeks. Patients with indications for cytoreductive therapy. During screening, female hemoglobin (HGB) ≥10g/dL, male hemoglobin (HGB) ≥11g/dL; neutrophil count ≥1.5×109/L; platelet count ≥100×109/L. Voluntary written informed consent. Exclusion Criteria: Symptomatic splenomegaly; Contraindications to interferon or ruxolitinib therapy; Severe or significant comorbidities that may affect the participant's ability to participate in the study, as determined by the investigator; History of major organ transplantation; Pregnant or breastfeeding women; History or current diagnosis of autoimmune thyroid disease (patients with controlled hypothyroidism on oral thyroid hormone replacement therapy may be included); Documented evidence of any other autoimmune disease (such as active hepatitis, systemic lupus erythematosus, antiphospholipid antibody syndrome, or autoimmune arthritis); Clinically significant bacterial, fungal, mycobacterial, parasitic, or viral infection such as active hepatitis or HIV infection (patients with acute bacterial infections requiring antibiotic treatment should be deferred from screening/enrollment until completion of antibiotic treatment); Evidence of severe retinopathy or clinically significant ophthalmologic disease (due to diabetes or hypertension); Current clinically significant depression or history of depression, or any suicidal attempt or tendency during screening; Active bleeding or thrombotic complications; History of any malignant tumor within the past 5 years (except for stage 0 chronic lymphocytic leukemia [CLL], cured basal cell carcinoma, squamous cell carcinoma, and superficial melanoma); History of alcohol or substance abuse within the past year; Presence of blasts in the peripheral blood within the past 3 months; Use of any investigational drug or participation in any other clinical trial within 4 weeks prior to the first dose of the study drug, or failure to recover from any effects of previously administered study drugs; The investigator deems the presence of any concurrent condition that may jeopardize the safety of the participant or the compliance to the protocol.

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

pegylated interferon α-2b in combination with ruxolitinib group

Pegylated interferon α-2b group

Arm Description

Pegylated interferon α-2b in combination with ruxolitinib group: Pegylated interferon α-2b at a starting dose of 180ug, subcutaneous injection once a week; ruxolitinib at a starting dose of 10mg, orally administered twice daily.

Pegylated interferon α-2b group: Starting dose of 180ug, subcutaneous injection once a week. If complete hematological remission is not achieved after 12 weeks of treatment with pegylated interferon α-2b alone, cross-over to the pegylated interferon α-2b plus ruxolitinib group is allowed; if ruxolitinib is not tolerated, cross-over to the pegylated interferon α-2b alone group is allowed.

Outcomes

Primary Outcome Measures

The cumulative complete hematologic response (CHR) rate
The proportion of patients who can achieve CHR ( defined as hematocrit lower than 45% without phlebotomies; platelet count < 400×109/L, WBC count < 10×109/L for at least 12 weeks) among all patients.

Secondary Outcome Measures

Cumulative CHR rates at Week 36.
Cumulative CHR rates at Week 36 will be compared between the two groups.
Cumulative CHR rates at Week 52.
Cumulative CHR rates at Week 52 will be compared between the two groups.
Time to CHR
The time of reaching CHR will be compared between the two groups.
The CHR rates after crossover
The CHR rates within 52 weeks after crossover
The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden.
The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden will be compared between the two groups.
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.
Change of splenomegaly
All subjects with palpable splenomegaly at baseline will undergo ultrasound examination. For subjects with palpable splenomegaly at baseline: Improvement - no palpable splenomegaly during clinical treatment visits; No progress - ultrasound examination during clinical treatment visits shows an increase in spleen size of ≤ 25%; Progress - Ultrasound examination during clinical treatment visits shows an increase in spleen size of>25%.
Change of bone marrow pathology
Bone marrow histological remission defined as the presence of age-adjusted normocellularity and disappearance of trilinear hyperplasia, and absence of grade 1 reticulin fibrosis; no remission defined as the persistence of trilinear hyperplasia; progression defined as disease transformation into post-PV myelofibrosis, myelodysplastic syndrome or acute leukemia.
The incidence of major thrombotic events
To compare the incidence of major thrombotic events between the two groups.
The incidence of major bleeding events
To compare the incidence of major bleeding events between the two groups.
The incidence of progressing to acute leukemia
The incidence of progressing to acute leukemia will be compared between the two groups.
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.
Change of quality of life using QLQ-C30 V3.0 questionnaire.
The QLQ-C30 V3.0 questionnaire consists of 30 questions, with questions 1-28 scoring 1-4 and questions 29 and 30 scoring 1-7. Therefore, this questionnaire has a minimum score of 30 and a maximum score of 126, and the score is directly proportional to the quality of life.
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
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, infection,

Full Information

First Posted
April 10, 2023
Last Updated
May 19, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05870475
Brief Title
Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV
Acronym
PV
Official Title
A Randomized Controlled Study Evaluating the Efficacy and Safety of Pegylated Interferon α-2b in Combination With Ruxolitinib vs. Pegylated Interferon α-2b Monotherapy for Treating Hydroxyurea-resistant/Intolerant Polycythemia Vera
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 30, 2023 (Anticipated)
Primary Completion Date
March 31, 2028 (Anticipated)
Study Completion Date
May 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Study purpose: To compare the efficacy and safety of pegylated interferon α-2b in combination with ruxolitinib versus pegylated interferon α-2b alone for treating hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera.
Detailed Description
Study purpose: To compare the efficacy and safety of pegylated interferon α-2b in combination with ruxolitinib versus pegylated interferon α-2b alone for treating hydroxyurea-resistant or hydroxyurea-intolerant polycythemia vera. The subjects will be randomly divided into two groups: pegylated interferon alpha-2b combined with ruxolitinib group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week; ruxolitinib at a starting dose of 10mg will be administered orally twice daily. pegylated interferon alpha-2b group: pegylated interferon alpha-2b at a starting dose of 180ug will be administered subcutaneously once a week. If complete hematologic remission is not achieved after 12 weeks of treatment with pegylated interferon alpha-2b alone, the subject may be switched to the pegylated interferon alpha-2b combined with ruxolitinib group. If ruxolitinib is not tolerated, the subject may be switched to the pegylated interferon alpha-2b group alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pegylated interferon α-2b in combination with ruxolitinib group
Arm Type
Experimental
Arm Description
Pegylated interferon α-2b in combination with ruxolitinib group: Pegylated interferon α-2b at a starting dose of 180ug, subcutaneous injection once a week; ruxolitinib at a starting dose of 10mg, orally administered twice daily.
Arm Title
Pegylated interferon α-2b group
Arm Type
Active Comparator
Arm Description
Pegylated interferon α-2b group: Starting dose of 180ug, subcutaneous injection once a week. If complete hematological remission is not achieved after 12 weeks of treatment with pegylated interferon α-2b alone, cross-over to the pegylated interferon α-2b plus ruxolitinib group is allowed; if ruxolitinib is not tolerated, cross-over to the pegylated interferon α-2b alone group is allowed.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
RUX
Intervention Description
Ruxolitinib at a starting dose of 10mg, orally administered twice daily. If ruxolitinib is not tolerated, cross-over to the pegylated interferon α-2b alone group is allowed.
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon α-2b
Other Intervention Name(s)
PEG IFNα-2b
Intervention Description
Starting dose of 180ug, subcutaneous injection once a week. If complete hematological remission is not achieved after 12 weeks of treatment with pegylated interferon α-2b alone, cross-over to the pegylated interferon α-2b plus ruxolitinib group is allowed.
Primary Outcome Measure Information:
Title
The cumulative complete hematologic response (CHR) rate
Description
The proportion of patients who can achieve CHR ( defined as hematocrit lower than 45% without phlebotomies; platelet count < 400×109/L, WBC count < 10×109/L for at least 12 weeks) among all patients.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 24.
Secondary Outcome Measure Information:
Title
Cumulative CHR rates at Week 36.
Description
Cumulative CHR rates at Week 36 will be compared between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 36.
Title
Cumulative CHR rates at Week 52.
Description
Cumulative CHR rates at Week 52 will be compared between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Time to CHR
Description
The time of reaching CHR will be compared between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
The CHR rates after crossover
Description
The CHR rates within 52 weeks after crossover
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden.
Description
The rate of reduction in JAK2V617F, CALR, or MPL gene mutation burden will be compared between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Impact of therapy on non-driver mutations
Description
To compare the proportion of subjects that display change on key non-driver biomarkers of the disease-DNMT3A, ASXL1, TET2 or other mutations.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Change of splenomegaly
Description
All subjects with palpable splenomegaly at baseline will undergo ultrasound examination. For subjects with palpable splenomegaly at baseline: Improvement - no palpable splenomegaly during clinical treatment visits; No progress - ultrasound examination during clinical treatment visits shows an increase in spleen size of ≤ 25%; Progress - Ultrasound examination during clinical treatment visits shows an increase in spleen size of>25%.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.]
Title
Change of bone marrow pathology
Description
Bone marrow histological remission defined as the presence of age-adjusted normocellularity and disappearance of trilinear hyperplasia, and absence of grade 1 reticulin fibrosis; no remission defined as the persistence of trilinear hyperplasia; progression defined as disease transformation into post-PV myelofibrosis, myelodysplastic syndrome or acute leukemia.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52
Title
The incidence of major thrombotic events
Description
To compare the incidence of major thrombotic events between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
The incidence of major bleeding events
Description
To compare the incidence of major bleeding events between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
The incidence of progressing to acute leukemia
Description
The incidence of progressing to acute leukemia will be compared between the two groups.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Change in Myeloproliferative Neoplasm Symptom Assessment Form total symptom score
Description
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.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Change of quality of life using QLQ-C30 V3.0 questionnaire.
Description
The QLQ-C30 V3.0 questionnaire consists of 30 questions, with questions 1-28 scoring 1-4 and questions 29 and 30 scoring 1-7. Therefore, this questionnaire has a minimum score of 30 and a maximum score of 126, and the score is directly proportional to the quality of life.
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Change of microcirculation disturbance
Description
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
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Specific pre-defined toxicity
Description
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, infection,
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Other Pre-specified Outcome Measures:
Title
Changes of T lymphocytes
Description
Change in the proportion and gene expression profile of T lymphocytes
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Changes of B lymphocytes
Description
Change in the proportion and gene expression profile of B lymphocytes
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.
Title
Changes of dendritic cells
Description
Change in the proportion and gene expression profile of dendritic cells
Time Frame
From the start of study treatment (Week 0) up to the end of Week 52.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years old. Male or Female. Meets the diagnostic criteria for Polycythemia Vera according to WHO-2022. Resistant or intolerant to hydroxyurea (based on the 2013 European LeukemiaNet criteria). Have not previously received interferon preparations or ruxolitinib treatment, or the washout period between the last use of interferon preparations or ruxolitinib and the first use of the study drug should not be less than 4 weeks. Patients with indications for cytoreductive therapy. During screening, female hemoglobin (HGB) ≥10g/dL, male hemoglobin (HGB) ≥11g/dL; neutrophil count ≥1.5×109/L; platelet count ≥100×109/L. Voluntary written informed consent. Exclusion Criteria: Symptomatic splenomegaly; Contraindications to interferon or ruxolitinib therapy; Severe or significant comorbidities that may affect the participant's ability to participate in the study, as determined by the investigator; History of major organ transplantation; Pregnant or breastfeeding women; History or current diagnosis of autoimmune thyroid disease (patients with controlled hypothyroidism on oral thyroid hormone replacement therapy may be included); Documented evidence of any other autoimmune disease (such as active hepatitis, systemic lupus erythematosus, antiphospholipid antibody syndrome, or autoimmune arthritis); Clinically significant bacterial, fungal, mycobacterial, parasitic, or viral infection such as active hepatitis or HIV infection (patients with acute bacterial infections requiring antibiotic treatment should be deferred from screening/enrollment until completion of antibiotic treatment); Evidence of severe retinopathy or clinically significant ophthalmologic disease (due to diabetes or hypertension); Current clinically significant depression or history of depression, or any suicidal attempt or tendency during screening; Active bleeding or thrombotic complications; History of any malignant tumor within the past 5 years (except for stage 0 chronic lymphocytic leukemia [CLL], cured basal cell carcinoma, squamous cell carcinoma, and superficial melanoma); History of alcohol or substance abuse within the past year; Presence of blasts in the peripheral blood within the past 3 months; Use of any investigational drug or participation in any other clinical trial within 4 weeks prior to the first dose of the study drug, or failure to recover from any effects of previously administered study drugs; The investigator deems the presence of any concurrent condition that may jeopardize the safety of the participant or the compliance to the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang, MD
Phone
8602223909240
Email
zhanglei1@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, MD
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, MD
Phone
8602223909240
Email
zhanglei1@ihcams.ac.cn

12. IPD Sharing Statement

Learn more about this trial

Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV

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