Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis
Condition: Myelofibrosis
MeSH terms: Primary Myelofibrosis
Intervention: Peginterferon alfa-2a
Intervention description: 50 mcg subcutaneous injection once per week
Intervention MeSH terms: Interferons; Interferon-alpha; Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary myelofibrosis; PMF

Summary:

      The purpose of this study is to look at the effectiveness of giving patients who have been
      newly diagnosed with untreated early stage primary myelofibrosis (PMF) a study drug called
      PEGINTRON (also known as pegylated interferon alfa 2b). This intervention will be compared to
      the widely employed "watch and wait" (best supportive care) approach for early stage PMF, in
      which patients are followed closely and treatment initiated only if the disease progresses.
    

Eligibility criteria:

        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

          1. 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)

          2. Not meeting WHO criteria for Polycythemia Vera (PV), Chronic Myeloid Leukemia (CML),
             Myledysplastic Syndrome (MDS), or other myeloid neoplasm

          3. 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

          1. Leukoerythroblastosis

          2. increase in serum Lactase Dehydrogenase (LDH)

          3. Anemia

          4. 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.