Sotatercept in Treating Patients With Myeloproliferative Neoplasm-Associated Myelofibrosis or Anemia
Condition: Anemia; Myelodysplastic/Myeloproliferative Neoplasm; Myelofibrosis
MeSH terms: Neoplasms; Anemia; Primary Myelofibrosis; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases
Intervention: Sotatercept; Ruxolitinib
Intervention description: Given SC
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of and how well sotatercept works in treating
      patients with myeloproliferative neoplasm-associated myelofibrosis or anemia. Sotatercept may
      stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  MPN-associated myelofibrosis

          -  Anemic patient OR red blood cell (RBC)-transfusion-dependent patient

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and
             aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
             equal to or less than 2.5 x upper limit of normal (ULN), or equal to or less than 4 x
             ULN (if upon judgment of the treating physician, it is believed to be due to
             extramedullary hematopoiesis [EMH] related to myelofibrosis [MF])

          -  Direct bilirubin equal to or less than 1.5 x ULN; or equal to or less than 2 x ULN (if
             upon judgment of the treating physician, it is believed to be due to extramedullary
             hematopoiesis related to MF)

          -  Creatinine clearance equal to or more than 50 mL/min

          -  Treatment-related toxicities from prior therapies must have resolved to grade equal to
             or less than 1

          -  Women of childbearing potential and men must agree to using medically approved (i.e.,
             mechanical or pharmacological) contraceptive measure for at least 112 days following
             the last dose of sotatercept (ACE-011); males must agree to use a latex condom or
             non-latex condom NOT made of natural (animal) membrane during any sexual contact with
             females of childbearing potential or a pregnant female while participating in the
             study and for at least 112 days following the last dose of sotatercept (ACE-011), even
             if he has a vasectomy

          -  For cohort of patients that are already on ruxolitinib therapy: on therapy with
             ruxolitinib for at least for 6 months, and on stable dose for last 2 months, before
             starting therapy with sotatercept

        Exclusion Criteria:

          -  Serious medical condition or psychiatric illness that would prevent, (as judged by the
             treating physician) the subject from signing the informed consent form or any
             condition including the presence of laboratory abnormalities, which places the subject
             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 female

          -  Known positive for human immunodeficiency virus-1 (HIV-1), or active infection with
             hepatitis-B or -C

          -  Use of any MPN-associated myelofibrosis-directed therapy within 2 weeks prior to study
             day 1 (other than ruxolitinib at a stable dose for patients in the combination cohort
             as stated in inclusion criteria)

          -  Symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia

          -  Prior sotatercept

          -  Major surgery within 4 weeks prior to day 1

          -  Severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins
             or excipients in the investigational product

          -  Uncontrolled hypertension (systolic blood pressure [SBP] equal to or more than 140 or
             diastolic blood pressure [DBP] equal to or more than 90)