Clinical Trials /

P1101 in Treating Patients With Myelofibrosis

NCT02370329

Description:

This pilot phase II trial studies P1101 (polyethyleneglycol [PEG]-proline-interferon alpha-2b) in treating patients with myelofibrosis. PEG-proline-interferon alpha-2b is a substance that can improve the body's natural response and may slow the growth of myelofibrosis.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: P1101 in Treating Patients With Myelofibrosis
  • Official Title: Phase II Study of P1101 in Early Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: MC138F
  • SECONDARY ID: NCI-2015-00183
  • SECONDARY ID: MC138F
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02370329

Conditions

  • Primary Myelofibrosis
  • Secondary Myelofibrosis

Interventions

DrugSynonymsArms
PEG-Proline-Interferon Alfa-2bAOP2014, P1101, PEG-P-IFN-Alfa-2b, PEG-P-IFN-Alpha-2bTreatment (PEG-proline-interferon alpha-2b)

Purpose

This pilot phase II trial studies P1101 (polyethyleneglycol [PEG]-proline-interferon alpha-2b) in treating patients with myelofibrosis. PEG-proline-interferon alpha-2b is a substance that can improve the body's natural response and may slow the growth of myelofibrosis.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate for clinical response (complete remission [CR], partial remission [PR], or
      clinical improvement [CI]) as defined by International Working Group-Myeloproliferative
      Neoplasms Research and Treatment (IWG-MRT) criteria in a cohort of intermediate-2/high risk
      myelofibrosis (MF) patients. Response in a second cohort of early stage MF patients will
      also be described.

      SECONDARY OBJECTIVES:

      I. To evaluate the adverse event profile of P1101 in patients with myelofibrosis by cohort
      (early vs intermediate-2/high risk).

      II. To evaluate the tolerability of P1101 in patients with myelofibrosis by cohort (early vs
      intermediate-2/high risk).

      TERTIARY OBJECTIVES:

      I. To evaluate quality of life (QOL) and patient-reported symptoms using the
      Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) with P1101 for patients with
      myelofibrosis by cohort (early vs intermediate-2/high risk).

      II. To evaluate the impact of P1101 on bone marrow and histological features of
      myelofibrosis including cytogenetics, blast percentage, fibrosis, and JAK2-V617F allele
      burden by cohort (early vs intermediate-2/high risk).

      OUTLINE:

      Patients receive PEG-proline-interferon alpha-2b subcutaneously (SC) on days 1 and 15.
      Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3-6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (PEG-proline-interferon alpha-2b)ExperimentalPatients receive PEG-proline-interferon alpha-2b SC on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Evaluable myelofibrosis by IWG-MRT criteria including one or more of the following:
    
                   -  Spleen >= 5 cm below the left costal margin
    
                   -  MPN-SAF total symptom score (TSS) > 10 at baseline
    
                   -  Hemoglobin < 10 g/dL
    
              -  Confirmed diagnosis of myelofibrosis (primary myelofibrosis or myelofibrosis
                 secondary to essential thrombocythemia or polycythemia vera) by World Health
                 Organization (WHO) diagnostic criteria (3 major and 2 minor criteria: major criteria:
                 megakaryocyte proliferation and atypia with either reticulin and/or collagen
                 fibrosis, not meeting criteria for chronic myelogenous leukemia [CML], polycythemia
                 vera [PV], myelodysplastic syndrome [MDS], or other myeloid neoplasm, JAK2V617F or
                 other clonal marker or no evidence of reactive marrow fibrosis; minor criteria:
                 leukoerythroblastosis, increased lactate dehydrogenase [LDH], anemia, palpable
                 splenomegaly)
    
              -  For cohort 1: early stage MF (low or intermediate 1 stage as defined by Dynamic
                 International Prognostic Scoring System [DIPSS]) without currently available
                 treatment options
    
              -  For cohort 2: intermediate-2 or high risk MF patients as defined by DIPSS either not
                 eligible for ruxolitinib or having failed under ruxolitinib
    
              -  No prior treatment for myelofibrosis (for cohort 1 only)
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
    
              -  Platelet count >= 100,000/mm^3
    
              -  Absolute neutrophil count (ANC) >= 1000/mm^3
    
              -  Aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN)
    
              -  Alanine aminotransferase (ALT) =< 2.5 x ULN
    
              -  Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault
                 formula
    
              -  Negative pregnancy test done =< 7 days prior to registration, for women of
                 childbearing potential only
    
              -  Ability to complete questionnaire(s) by themselves or with assistance
    
              -  Provide informed written consent
    
              -  Willing to return to enrolling institution for follow-up
    
              -  Willing to provide blood samples for correlative research purposes
    
            Exclusion Criteria:
    
              -  Patients who have had chemotherapy or radiation =< 2 weeks of registration
    
              -  For cohort 1 only: patients with evidence of intermediate 2 or high risk disease
                 (according to DIPSS)
    
              -  For cohort 1 only: patients with a bone marrow biopsy with < 15% cellularity,
                 evidence of collagen fibrosis, osteosclerosis, or blasts > 10% in peripheral blood or
                 marrow (demonstrating advanced disease)
    
              -  Patients who have received a prior stem cell transplant
    
              -  Patients who have received radiation to the spleen within 3 months prior to
                 registration
    
              -  Patients with intolerance to compounds similar to pegylated interferon alpha-2b
    
              -  Patients with evidence of >= grade 2 peripheral sensory neuropathy
    
              -  Any of the following:
    
                   -  Pregnant women
    
                   -  Nursing women
    
                   -  Men or women of childbearing potential who are unwilling to employ adequate
                      contraception
    
              -  Co-morbid systemic illnesses or other severe concurrent disease which, in the
                 judgment of the investigator, would make the patient inappropriate for entry into
                 this study or interfere significantly with the proper assessment of safety and
                 toxicity of the prescribed regimens
    
              -  Immunocompromised patients or patients known to be human immunodeficiency virus (HIV)
                 positive and currently receiving antiretroviral therapy
    
              -  Uncontrolled simultaneous illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, history of depression, or psychiatric illness/social situations that
                 would limit compliance with study requirements
    
              -  Receiving any other investigational agent which would be considered as a treatment
                 for the primary neoplasm
    
              -  History of myocardial infarction =< 6 months prior to registration, or congestive
                 heart failure requiring use of ongoing maintenance therapy for life-threatening
                 ventricular arrhythmias
    
              -  History of significant or major funduscopic findings including, but not limited to,
                 retinal exudates, hemorrhage, detachment, neovascularization, papilledema, optic
                 atrophy, micro-aneurysm or macular changes
    
              -  Other active malignancy at time of registration; EXCEPTIONS: non-melanotic skin
                 cancer or carcinoma-in-situ of the cervix
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Best overall response (CR, PR, or CI) as determined by International Working Group Criteria
    Time Frame:Up to 3 years
    Safety Issue:
    Description:The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

    Secondary Outcome Measures

    Measure:Incidence of adverse events, as measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4)
    Time Frame:Up to 3 years
    Safety Issue:
    Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
    Measure:Survival time
    Time Frame:Time from registration to death due to any cause, assessed up to 3 years
    Safety Issue:
    Description:The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Mayo Clinic

    Last Updated

    October 6, 2016