Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis
Condition: Myelofibrosis
MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential
Intervention: Simtuzumab; Ruxolitinib
Intervention description: Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks; In Stage 2, participants will be on a stable dose of ruxolitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hematology; Myelofibrosis; Thrombocythemia Myelofibrosis; Bone Marrow Diseases; Hematologic Diseases; Blood Diseases; Leukemia; Blood Disorders

Summary:

      This study is to evaluate the efficacy and safety of simtuzumab (GS-6624) on bone marrow
      fibrosis either alone or in combination with ruxolitinib in participants with primary
      myelofibrosis (PMF) and post polycythemia vera or post essential thrombocythemia
      myelofibrosis (ET/PV MF).

      The study is designed as a two-stage trial. In the stage 1, participants will be randomized
      into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, participants
      on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or
             high risk disease according to the international working group (IWG) prognostic
             scoring system, or if with low risk disease then with symptomatic splenomegaly that is
             ≥ 10 cm below left costal margin by physical exam.

          -  Must have adequate organ function as demonstrated by the following:

          -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5x upper
             limit of normal (ULN), or ≤ 4x ULN (if upon judgment of the treating physician, it is
             believed to be due to extramedullary hematopoiesis [EMH] related to MF);

          -  Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician,
             it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);

          -  Serum creatinine ≤ 2.5 mg/dL.

          -  In Stage 2, participants must be on ruxolitinib for at least 8 weeks and on a stable
             dose for at least 4 weeks.

          -  Eastern cooperative oncology group (ECOG) performance status (PS) ≤ 2

          -  Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1

          -  Women of childbearing potential and men must agree to using one medically approved
             (ie, mechanical or pharmacological) contraceptive measure and have their partners
             agree to an additional barrier method of contraception for the duration of the study
             and for 90 days after the last administration of study drug. Definition of female of
             child bearing potential and a list of acceptable contraceptive methods for this study
             applies per protocol.

        Exclusion Criteria:

          -  Any serious medical condition or psychiatric illness that would prevent, (as judged by
             the treating physician) the participant from signing the informed consent form or any
             condition, including the presence of laboratory abnormalities, which places the
             participant at unacceptable risk if he/she were to participate in the study or
             confounds the ability to interpret data from the study.

          -  Pregnant or lactating.

          -  Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.

          -  History or presence of any form of cancer within the 3 years prior to enrollment, with
             the exception of excised basal cell or squamous cell carcinoma of the skin, or
             cervical carcinoma in situ or breast carcinoma in situ that has been excised or
             resected completely and is without evidence of local recurrence or metastasis.

          -  Participation in an investigational drug or device trial within 2 weeks prior to study
             Day 1 or within 5 times the half-life of the investigational agent in the other
             clinical study, if known.

          -  Use of any cytotoxic chemotherapeutic agents (eg, hydroxyurea), corticosteroids
             (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators
             (eg, thalidomide) within 2 weeks and interferon use within 4 weeks prior to study Day
             1.

          -  Symptomatic congestive heart failure (New York Heart Association Classification >
             Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.

          -  History of surgery within 2 weeks prior to enrollment or anticipated surgery during
             the study period.

          -  Any other condition that might reduce the chance of obtaining data required by the
             protocol or that might compromise the ability to give truly informed consent.