- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01758588
Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis
Phase II Randomized Controlled Trial of Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital
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New York
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New York, New York, United States, 10021
- Weill Medial College of Cornell Universiy
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must meet laboratory, and bone marrow histological criteria for primary myelofibrosis as defined by World Health Organization (WHO) diagnostic criteria as follows:
WHO diagnostic criteria for PMF Proposed Criteria for PMF Major Criteria
- Presence of megakaryocyte proliferation and atypia, usually accompanied by either reticulin and/or collagen fibrosis, or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (ie. prefibrotic cellular-phase disease)
- Not meeting WHO criteria for Polycythemia Vera (PV), Chronic Myeloid Leukemia (CML), Myledysplastic Syndrome (MDS), or other myeloid neoplasm
- Demonstration of JAK2617V>F or other clonal marker (e.g. MPL515W>L/K), or in the absence of a clonal marker, no evidence of bone marrow fibrosis due to underlying inflammatory or other neoplastic disease
Minor Criteria
- Leukoerythroblastosis
- increase in serum Lactase Dehydrogenase (LDH)
- Anemia
Palpable splenomegaly
- Patients must have Low or Intermediate 1 stage of disease as defined by International Working Group (IWG) risk stratification of primary myelofibrosis in the dynamic international prognostic scoring system (DIPSS). In addition, they must show some active hematopoiesis with a cellularity of at least 15%, irrespective of the degree of reticulin and/or collagen fibrosis as defined by Manoharan criteria.
- Patients should NOT have had prior therapy for primary myelofibrosis. This includes treatment with cytoreductive drugs (Hydroxyurea), immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), JAK2 inhibitors, or other therapies specifically for myelofibrosis. If they received these classes of drugs for indications other than PMF, treatment should be discontinued at least 6 weeks prior to randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
Patients must have normal organ and marrow function as defined below:
- White blood cell (WBC) ≥ 3,000/microL
- Absolute Neutrophil Count (ANC) ≥ 1,500/microL
- Platelets ≥ 100,000//microL
- Total bilirubin within normal limits
- Aspartate aminotransferase - serum glutamic oxaloacetic transaminase (AST(SGOT)) and alanine aminotransferase - serum glutamic pyruvic transaminase (ALT(SGPT)) less than or equal to 2.5 X upper limit of normal
- Creatinine Clearance ≥ 50 ml/min
- The effects of peg-IFNα-2b on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- Patients who have had chemotherapy or radiotherapy within 6 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 6 weeks earlier.
- Patients with Intermediate 2 or High risk stage of disease as defined by International Working Group (IWG) risk stratification of primary myelofibrosis in the dynamic international prognostic scoring system (DIPSS) and/or bone marrow biopsy showing less than 15% cellularity in the presence +2 or more reticulin fibrosis (by Manoharan criteria), collagen fibrosis, or osteosclerosis.
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to peg-IFNα-2b
Other Exclusion Criteria
- Female patients who are pregnant or breast feeding
- History of depression or active treatment for depression
- History of non-compliance to medical regimens
- History of autoimmune diseases
- History of hypothyroidism or hyperthyroidism
- Clinical evidence of neuropathy
- Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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No Intervention: Observation arm
Subjects will be monitored closely for disease progression, however will receive no intervention.
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Experimental: Peginterferon alfa-2a
Peginterferon alfa-2a will be administered at a dose of 50 micrograms once a week for up to 3 years.
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50 mcg subcutaneous injection once per week
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Improvement
Time Frame: One year
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Clinical improvement (CI) Requires one of the following in the absence of both disease progression (as outlined below) and Complete Response (CR)/Partial Response (PR) assignment (CI response is validated only if it lasts for no fewer than 8 weeks) i. A minimum 20-g/L increase in hemoglobin level or becoming transfusion independent (applicable only for patients with baseline hemoglobin level of less than 100 g/L). ii. Either a minimum 50% reduction in palpable splenomegaly of a spleen that is at least 10 cm at baseline or a spleen that is palpable at more than 5 cm at baseline becomes not palpable. iii. A minimum 100% increase in platelet count and an absolute platelet count of at least 50 000 109/L (applicable only for patients with baseline platelet count below 50 109/L). iv. A minimum 100% increase in Absolute Neutrophil Count (ANC) and an ANC of at least 0.5 109/L (applicable only for patients with baseline absolute neutrophil count below 1 109/L). |
One year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: Week 21
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Progression free survival is the measure of subject survival in the absence of disease progression. Disease progression is defined as progression to the next higher International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Dynamic International Prognostic Scoring System (DIPSS) stage from diagnosis. The IWG-MRT DIPSS stratifies primary myelofibrosis (PMF) into four risk categories (low, intermediate 1, intermediate 2, and high risk), based on 5 clinical factors; Age>65, Hemoglobin <10gm/dL, white blood cell (WBC)>25,000/uL, peripheral blasts>1%, and constitutional symptoms. Progression free survival will be assessed at 21 weeks from time of study entry. |
Week 21
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Overall Survival
Time Frame: Week 21
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Overall survival measures subject survival regardless of disease progression. Overall survival will be assessed at 21 weeks from time of study entry. |
Week 21
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Richard T Silver, M.D., Weill Medical College of Cornell University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1202012178
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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