Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis

NCT01758588 | Terminated Phase 2 Results DMC

• 1 other identifier: 1202012178
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Myelofibrosis

Keywords

Primary myelofibrosis; PMF

Outcome Measures

Primary Outcomes (1)

• Clinical Improvement

  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

Secondary Outcomes (2)

• Progression Free Survival

  Week 21

• Overall Survival

  Week 21

Study Arms (2)

Observation arm

NO INTERVENTION

Subjects will be monitored closely for disease progression, however will receive no intervention.

Peginterferon alfa-2a

EXPERIMENTAL

Peginterferon alfa-2a will be administered at a dose of 50 micrograms once a week for up to 3 years.

Drug: Peginterferon alfa-2a

Interventions

Peginterferon alfa-2a DRUG

50 mcg subcutaneous injection once per week

Also known as: PEGINTRON, Interferon alfa, IFNα-2b

Peginterferon alfa-2a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Weill Medial College of Cornell Universiy

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

peginterferon alfa-2a; peginterferon alfa-2b; Interferon-alpha

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Due to early termination of the trial, there is not enough data to evaluate All-Cause Mortality. Therefore, it is reported that 0 subjects were affected out of 8 subjects at risk.

Results Point of Contact

• Title: Assistant Director of Leukemia and BMT Clinical Trials
• Organization: Weill Cornell Medicine

ell2028@med.cornell.edu

646-962-9305

Study Officials

• Richard T Silver, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2012
• First Posted: January 1, 2013
• Study Start: January 1, 2013
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 24, 2018
• Results First Posted: July 24, 2018

Record last verified: 2018-06

Locations

US (2)