Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01758588
First received: December 24, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Myelofibrosis
Drug: Peginterferon alfa-2a
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Controlled Trial of Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Evidence of improved clinical status [ Time Frame: One year ] [ Designated as safety issue: No ]
    Improved clinical status is defined as clinical improvement (CI) in the response criteria of the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and is evaluated by blood and bone marrow tests performed every 4 weeks for one year.


Secondary Outcome Measures:
  • Progression free survival and overall survival [ Time Frame: One year ] [ Designated as safety issue: No ]
    Survival will be assessed at one year from time of study entry.


Estimated Enrollment: 47
Study Start Date: January 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Observation arm
Subjects will be monitored closely for disease progression, however will receive no intervention.
Experimental: Peginterferon alfa-2a
Peginterferon alfa-2a will be administered at a dose of 50 micrograms once a week for up to 3 years.
Drug: Peginterferon alfa-2a
50 mcg subcutaneous injection once per week
Other Name: PEGINTRON, Interferon alfa, IFNα-2b

Detailed Description:

Subjects will be randomized into one of the study groups: one in which subjects get treated with PEGINTRON and the other in which subjects are closely followed and get best supportive care until disease progression (the presently accepted standard approach for early disease). Subjects on the observation arm will be carefully monitored for clinical or laboratory progression of disease during scheduled study visits. However, they will not be treated with an active drug like Interferon alfa or others such as Hydroxyurea, Revlimid, Thalidomide, Pomalidomide, and the newly approved JAK2 inhibitor Ruxolitinib (Jakafi). If their disease progresses, they will be eligible for cross-over into the treatment arm with PEGINTRON. Subjects randomized to the treatment arm will receive PEGINTRON once weekly.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Patients must meet laboratory, and bone marrow histological criteria for primary myelofibrosis as defined by WHO diagnostic criteria as follows:

WHO diagnostic criteria for PMF18 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 PV, CML. 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 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 hematopoiesism with a cellularity of at least 15%, irrespective of the degree of reticulin and/or collagen fibrosis as defined by Manoharan criteria49.
    • 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.
    • ECOG performance status < 2
    • Patients must have normal organ and marrow function as defined below:

      • WBC ≥ 3,000/microL
      • ANC ≥ 1,500/microL
      • platelets ≥ 100,000//microL
      • total bilirubin within normal limits
      • AST(SGOT)/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)49, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01758588

Contacts
Contact: Richard T Silver, M.D. 646-962-2273 rtsilve@med.cornell.edu

Locations
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Wilena Session    404-778-5319    wilena.s.session@emory.edu   
Principal Investigator: Elliott Winton, MD         
United States, New York
Weill Medial College of Cornell Universiy Recruiting
New York, New York, United States, 10021
Contact: Ruth Baumann, R.N.    212-746-4882    rub9018@med.cornell.edu   
Principal Investigator: Richard T Silver, M.D.         
Sub-Investigator: Ellen K Ritchie, M.D.         
Sub-Investigator: Gail Roboz, M.D.         
Sub-Investigator: Eric Feldman, M.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Richard T Silver, M.D. Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01758588     History of Changes
Other Study ID Numbers: 1202012178
Study First Received: December 24, 2012
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Primary myelofibrosis
PMF

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Interferons
Interferon-alpha
Peginterferon alfa-2a
Peginterferon alfa-2b
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014