Clinical trial NCT01758588: Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis
Official title: Phase II Randomized Controlled Trial of Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelofibrosis
Keywords: Primary myelofibrosis
PMF
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2013-01-01
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 (Janus Kinase 2) 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 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.

Primary outcomes:
measure: Clinical Improvement
timeFrame: One year
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Week 21
measure: Overall Survival
timeFrame: Week 21
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: New York
country: United States
facility: Weill Medial College of Cornell Universiy
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Richard T Silver, M.D.
role: PRINCIPAL_INVESTIGATOR
References: